BIOM 3000 Lecture Notes PDF

BIOM 3000 - lecture notes Lecture 1 Neuroanatomy: Study of the anatomy and organization of the central nervous system (CNS). Neuroanatomical Terminology: ○ Planes: Coronal (front & back), Sagittal (left & right), Horizontal (top & bottom). ○...

BIOM 3000 - lecture notes Lecture 1 Neuroanatomy: Study of the anatomy and organization of the central nervous system (CNS). Neuroanatomical Terminology: ○ Planes: Coronal (front & back), Sagittal (left & right), Horizontal (top & bottom). ○ Directional Terms: Anterior/Posterior (front/back), Medial/Lateral (inside/outside), Superior/Inferior (top/bottom), Dorsal/Ventral (top/bottom), Rostral/Caudal (front/back). Nervous System Classification: 1. Central Nervous System (CNS): ○ Brain & spinal cord. ○ White matter: myelinated axons. ○ Gray matter: cell bodies & dendrites. 2. Peripheral Nervous System (PNS): ○ Divided into autonomic (sympathetic, parasympathetic) and somatic systems. Cells of the Nervous System: 1. Neurons: ○ Convey information through electrical & chemical signals. ○ Functional unit of behavior, but with limited ability to be replaced. 2. Glial Cells: ○ Support system for neurons, crucial for neuronal function. ○ Types: Schwann Cells: Myelinate axons in the PNS, support axon regeneration.  Oligodendrocytes: Myelinate axons in the CNS, with multiple processes covering multiple axons. Astrocytes: Most abundant glial cell in the CNS, provide metabolic support, regulate extracellular fluid, and participate in CNS injury response. Microglia: Smallest glial cells, function in immune response, transforming into macrophages to clear debris. Ependymal Cells: Line the brain’s ventricles and spinal canal, help move and produce cerebrospinal fluid (CSF). Neuron Morphology: Parts of Neuron: ○ Dendrites: Receive signals. ○ Soma (Cell Body): Synthesis of macromolecules, integration of electrical signals. ○ Axon: Conducts action potentials. ○ Axon Terminal: Involved in neurotransmission. Neuron Classification: Structure: Unipolar, Pseudo-unipolar, Bipolar, Multipolar. Function: Sensory (afferent), Motor (efferent), Autonomic (preganglionic/postganglionic), Interneuron, Projection. Visualizing Neurons: 1. Golgi Staining: ○ Stains a limited number of cells randomly. ○ Developed by Camillo Golgi and used by Santiago Ramón y Cajal (Nobel Prize winners). 2. Immunohistochemistry: ○ Uses antibodies to visualize specific proteins in neurons and glia (e.g., NeuN for neurons, GFAP for astrocytes). 3. Neuron Filling: ○ Injection methods to trace neuronal pathways using substances like GFP, biotin, or viruses. Glial Cells and Their Functions 1. Schwann Cells (PNS) ○ Principal glial cell of the Peripheral Nervous System (PNS) ○ Provides metabolic support to neurons. ○ Wraps around individual axons to form the myelin sheath, which acts as electrical insulation. ○ Involved in PNS axon regeneration after injury. 2. Oligodendrocytes (CNS) ○ The myelinating cells of the Central Nervous System (CNS). ○ A single oligodendrocyte can extend multiple processes to surround and myelinate several axons at once. 3. Astrocytes (CNS) ○ The most abundant glial cell in the CNS (comprising 75% of glial cells).  ○ Provides mechanical support and metabolic support (stores glycogen). ○ Helps in the regulation of extracellular fluid by controlling levels of K+ ions and neurotransmitters. ○ Contacts blood vessels in the CNS, aiding in blood-brain barrier maintenance. ○ Responds to injury or insult by becoming reactive astrocytes. 4. Microglia (CNS) ○ The smallest glial cells, making up about 10-15% of the CNS. ○ Plays a major role in responding to CNS injury by surveying for damage or disease. ○ Activated by inflammation, they transform into macrophages (phagocytic cells) to remove debris. 5. Ependymal Cells ○ Line the ventricles of the brain and the central canal of the spinal cord. ○ Have cilia to aid in the movement of cerebrospinal fluid (CSF). ○ Specialized ependymal cells in the choroid plexus are responsible for CSF production. ○ May have a regenerative role. Lecture 2 Neuron and Nervous System Function Notes From the last lecture… 1. Parts of a Neuron: ○ Dendrites: Receive signals from other neurons. ○ Cell Body (Soma): Contains the nucleus and metabolic machinery of the cell. ○ Axon: Transmits electrical impulses (action potentials) from the cell body. ○ Axon Hillock: Initiates action potentials. ○ Synaptic Terminals: Release neurotransmitters to communicate with other neurons. 2. Neuron Polarization: ○ Neurons are polarized because there is a difference in electrical charge across the cell membrane. This is due to ion distribution, with the inside of the neuron being more negative than the outside (~ -70 mV resting membrane potential). 3. Primary Role of Glial Cells: ○ Support and protect neurons, providing structural integrity, metabolic support, and regulating the extracellular environment (e.g., maintaining the blood-brain barrier, myelination, responding to injury). 4. Myelination: ○ Myelination refers to the process where glial cells (Schwann cells in the PNS, oligodendrocytes in the CNS) wrap around axons to form a myelin sheath, which speeds up electrical signal transmission and provides insulation. Ion Channels:  Properties: ○ Ion specificity: Each channel allows specific ions to pass. ○ Open/close in response to stimuli: Channels are sensitive to ligands, voltage, or mechanical stretch. ○ Passive ion movement: Ions move down their electrochemical gradients. Types: ○ Ligand-gated: Open in response to neurotransmitter binding. ○ Voltage-gated: Open/close due to changes in membrane potential. ○ Mechanical/stretch-gated: Respond to physical deformation. ○ Leak channels: Always open, contributing to resting membrane potential. Ionic Equilibrium & Resting Membrane Potential (RMP): RMP is the electrical potential across the neuron membrane when not firing (~ -70 mV). K+ diffusion and selective membrane permeability to ions (K+ and Cl-) establish the RMP. The Na+/K+ ATPase pump helps maintain ion gradients by actively transporting 3 Na+ out and 2 K+ into the cell. Action Potentials: Action potentials are rapid changes in membrane potential, propagated along the axon. Begin at the axon hillock where threshold is reached (summation of excitatory and inhibitory inputs). Voltage-gated Na+ channels open, causing depolarization, followed by the opening of voltage-gated K+ channels for repolarization. Properties of Action Potentials: 1. Threshold: Must be reached to trigger AP. 2. All-or-none event: AP either occurs fully or not at all. 3. Conduction without decay: AP travels without losing strength. 4. Refractory period: After an AP, a neuron cannot immediately fire another one. Action Potential Phases: 1. Depolarization: Opening of voltage-gated Na+ channels, Na+ rushes in. 2. Repolarization: Na+ channels close, K+ channels open, K+ exits. 3. Hyperpolarization: K+ channels stay open longer, making the membrane more negative than RMP. 1. Axon Hillock & Threshold Summation: The axon hillock integrates all excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) from presynaptic neurons to determine if the neuron will fire. ○ Temporal Summation: Summation of signals that occur closely in time. ○ Spatial Summation: Summation of signals from multiple synapses located at different positions on the neuron. Threshold: Once the neuron reaches a specific membrane potential (threshold), voltage-gated Na+ channels open, triggering an action potential. 2. Action Potential Phases Threshold: Initiates the action potential. Depolarization: Voltage-gated Na+ channels open, allowing Na+ influx, which makes the inside of the cell more positive. Repolarization: Voltage-gated Na+ channels close and voltage-gated K+ channels open, allowing K+ to exit the cell, restoring the negative membrane potential. Hyperpolarization: The cell becomes more negative than the resting potential as voltage-gated K+ channels remain open for a short period. 3. Refractory Periods Absolute Refractory Period: The neuron cannot fire another action potential regardless of the stimulus because Na+ channels are inactivated. Relative Refractory Period: The neuron can fire again but requires a stronger stimulus due to the cell being in a hyperpolarized state. This ensures that action potentials propagate in one direction. 4. The Synapse Synapse: A specialized junction between neurons (or between neurons and target organs) for communication. ○ Presynaptic Ending: Contains neurotransmitters. ○ Synaptic Cleft: The space between the presynaptic and postsynaptic neurons. ○ Postsynaptic Element: Contains receptors that respond to neurotransmitters. 5. Steps in Synaptic Transmission 1. Neurotransmitter Production: Neurotransmitters are synthesized either in the axon terminal (small molecule NTs) or in the cell body (peptide NTs). 2. Packing of Neurotransmitters: Neurotransmitters are packaged into vesicles.  3. Release of Neurotransmitters: Depolarization of the presynaptic terminal opens voltage-gated Ca2+ channels, triggering neurotransmitter release via exocytosis. 4. Binding to Receptors: Neurotransmitters diffuse across the synaptic cleft and bind to receptors on the postsynaptic membrane. 5. Termination of Neurotransmitter Action: Neurotransmitter effects are stopped by degradation, reuptake, or diffusion away from the synapse. 6. Neurotransmitter Synthesis Small Molecule NTs: Synthesized in the axon terminal by enzymes (e.g., acetylcholine via choline acetyltransferase). Peptide NTs: Synthesized as precursor peptides in the cell body and transported to the presynaptic terminal (e.g., Corticotrophin-releasing factor (CRF)). 7. Release of Neurotransmitters Ca2+-Mediated Secretion: When the presynaptic terminal depolarizes, voltage-gated Ca2+ channels open. Ca2+ influx causes vesicles to fuse with the presynaptic membrane, releasing neurotransmitters into the synaptic cleft. 8. Binding to Receptors Small Vesicle NTs: Rapidly diffuse across the synaptic cleft and bind quickly to receptors. Large Vesicle NTs: Have slower release and act on more distant receptors, leading to slower responses. Neurotransmitter Effects: Determined by the type of receptor on the postsynaptic membrane, which can prodFast or Slow responses. ○ Excitatory (EPSP) or Inhibitory (IPSP) outcomes, depending on the ion channels activated (Na+, K+, Cl-). 9. Termination of Neurotransmitter Action Rapid removal of neurotransmitters from the synaptic cleft is essential for the postsynaptic membrane to reset and prepare for the next signal. Mechanisms of Termination: 1. Reuptake by the presynaptic membrane or nearby glial cells: Neurotransmitters like serotonin, norepinephrine, and dopamine are taken back into the presynaptic neuron or adjacent glial cells. 2. Enzymatic Inactivation: Specific enzymes break down neurotransmitters in the synaptic cleft. Example: Acetylcholine is broken down by acetylcholinesterase (AChE). 3. Uptake by the Postsynaptic Terminal: Some neurotransmitters may be absorbed by the postsynaptic neuron. 4. Diffusion: Neurotransmitters can simply diffuse out of the synaptic cleft, reducing their concentration and effects. Lecture 3 2. Embryology - Germ Layers Endoderm: Forms the gut, liver, and lungs. Mesoderm: Forms skeleton, muscle, kidney, and heart. Ectoderm: Develops into skin and the nervous system. 3. Origins of CNS and PNS Development CNS: The mesoderm induces the ectoderm to form neuroectoderm, which gives rise to the neural plate and neural tube (develops into the brain and spinal cord). PNS: Derived from neural crest cells, neural tube (preganglionic autonomic nerves and motor neurons), and mesoderm (meninges and connective tissue around peripheral nerves). 4. Primary Neurulation Occurs in the 3rd to 4th week of development. The notochord (mesoderm) induces the ectoderm to differentiate into neuroectoderm, forming the neural plate, which folds into neural folds and fuses to create the neural tube. Neural crest cells form from the edges of the neural plate, contributing to the PNS. 5. Errors in Neurulation Spina Bifida: Incomplete closure of the caudal neural tube. ○ Occulta: Incomplete vertebrae closure (~5% of the population). ○ Meningocele: Meninges protrude outside the vertebrae. ○ Myelomeningocele: The spinal cord and meninges are outside in a sac-like structure. Most severe Encephalocele: Sac-like protrusion of brain tissue. Anencephaly: Incomplete closure of the rostral neural tube, leading to the absence of the telencephalon (cerebrum). 6. Early Neural Tube Structure Ventricular Zone: Contains neural progenitor cells, neuroblasts, and glioblasts. Intermediate/Mantle Zone: Contains neurons and glial cells, forms the gray matter.  Marginal Zone: Contains neuronal and glial processes, forming the white matter. 7. Spinal Cord Development Sulcus limitans separates sensory and motor regions: ○ Dorsal portion (Alar Plate): Sensory neurons. ○ Ventral portion (Basal Plate): Motor neurons. Dorsal Root Ganglion (DRG): Sends projections both centrally and peripherally. 8. Brain Development As the neural tube closes, it forms three primary vesicles: 1. Prosencephalon (forebrain). 2. Mesencephalon (midbrain). 3. Rhombencephalon (hindbrain). These primary vesicles further develop into secondary vesicles: Telencephalon: Forms the cerebral hemispheres. Diencephalon: Forms structures like the thalamus and hypothalamus. Mesencephalon: Becomes the midbrain. Metencephalon: Develops into the pons and cerebellum. Myelencephalon: Becomes the medulla oblongata. The telencephalon grows rapidly, forming a C-shaped arc around the insula. Development of the ventricular system is continuous with the spinal cord’s central canal. 9. Neuronal Proliferation and Migration Neurogenesis occurs in the ventricular zone (VZ). Radial Migration: Neuron migrate radially using radial glial cells as guides. Tangential Migration: Occurs from the medial and lateral ganglionic eminence, producing inhibitory cortical interneurons. Thalamus and corpus striatum develop first Corpus striatum “sliced” into caudate and lentiform/lenticular nucei by corticothalamic fibres 10. Regressive Events in Brain Development Programmed Cell Death (Apoptosis): Removes up to 70% of neurons in some cortical regions prenatally and eliminates excess oligodendrocytes postnatally. Synaptic Pruning: Excess synapses are produced, followed by the elimination of up to 50%, largely postnatal. 11. Neural Crest Cells - PNS Development Neural Crest Cells are highly proliferative and differentiate into neural and non-neural tissues, migrating throughout the embryo. Two Types: Cranial and Trunk Dorsal Root Ganglion (DRG) provides sensory input and synapses in the dorsal horn. 12. Autonomic Nervous System  Comprises a 2-neuron system (preganglionic and postganglionic). Sympathetic Nervous System: Fight or flight, neurons originate from the thoracic and lumbar spinal cord. Ach + Ne Parasympathetic Nervous System: Rest and digest, neurons originate from the brainstem and sacral spinal cord. Ach+ Ach 13. Nervous System Repair Peripheral Nervous System (PNS): Regeneration is possible with Schwann cell proliferation and axon regeneration. Central Nervous System (CNS): Limited repair capacity, with obstacles like astrocyte scarring and inhibitory molecules (e.g., CSPGs). Some adult neurogenesis occurs in the subgranular zone and subventricular zone. Lecture 4 Learning Outcomes By the end of the lecture, students will be able to: 1. Identify the 5 major lobes of the cerebrum and explain their basic functions. 2. List the major internal cerebral nuclei. 3. Describe the divisions of the diencephalon and brainstem. 4. Describe the 3 meningeal layers and differentiate between the cranial and spinal meninges. Neuroanatomical Terminology Major CNS Divisions Seen in a mid-sagittal section of the brain, dividing it into its core components. Note: Mouse and Rabit have smooth brains, very little gyri and sulci Cerebrum Connectivity Corpus callosum: A large bundle of nerve fibers that interconnects most cortical areas of the two cerebral hemispheres. Anterior commissure: Connects temporal lobe regions across both hemispheres. Sulci and Gyri Sulcus (Sulci): Grooves or depressions on the surface of the brain. ○ Deep sulci are referred to as fissures. Gyrus (Gyri): Raised ridges or folds between two sulci. They increase the surface area of the cortex and act as important landmarks. Major Sulci 4 Major Sulci (Grooves): ○ Lateral surface: Central sulcus (of Rolando): Divides the frontal and parietal lobes. Lateral sulcus (Sylvian fissure): Separates the frontal and temporal lobes. ○ Medial surface: Parietooccipital sulcus: Divides the parietal and occipital lobes. Cingulate sulcus: Runs along the medial surface, above the cingulate gyrus. + Sulci Names: Many are named based on their location within the cerebral lobes or in relation to other major sulci. Gyri Gyri are named based on the sulci (grooves) they are adjacent to. ○ Examples: Precentral gyrus: Located before the central sulcus. Postcentral gyrus: Located after the central sulcus. Superior, middle, and inferior frontal gyri: Located in the frontal lobe and correspond to different functional areas of the brain.Lobes of the Cerebrum The cerebral lobes are defined by 4 major sulci: ○ Frontal lobe (pink) ○ Parietal lobe (blue) ○ Occipital lobe (yellow) ○ Temporal lobe (green) ○ Limbic lobe (purple) Major sulci include: ○ Cingulate sulcus ○ Parietooccipital sulcus ○ Central sulcus ○ Sylvian fissure (lateral sulcus) Functional Anatomy of the Cerebrum Frontal Lobe: ○ Involved in motor functions. The precentral gyrus contains the primary motor cortex. ○ Broca’s area: Responsible for the production of written and spoken language. Parietal Lobe: ○ Processes somatosensory information. The postcentral gyrus contains the primary somatosensory cortex. Occipital Lobe: ○ Involved in vision. Contains the primary visual cortex and visual association areas. Temporal Lobe: ○ Superior temporal gyrus contains the primary auditory cortex. ○ Wernicke’s area: Important for language comprehension. The Limbic Lobe (System) The limbic system includes telencephalic (cerebral) structures and diencephalic structures. ○ Telencephalon structures: Cingulate gyrus Parahippocampal gyrus Hippocampus Amygdala ○ Diencephalon structures: Thalamus Hypothalamus ○ Functions: Plays a critical role in emotional responses and memory. Limbic System & Internal Cerebral Anatomy Limbic System Nuclei: ○ Amygdala (Am): Involved in emotional responses, especially fear. ○ Hippocampus (HC): Critical for memory formation and spatial navigation. Basal Ganglia: ○ Globus pallidus (GP): Involved in regulating voluntary movement. ○ Caudate (C): Plays a role in learning and memory. ○ Putamen (P): Involved in motor control and influences various types of learning. Diencephalon: ○ Thalamus (Th): Acts as the gatekeeper for sensory information (except olfaction) en route to the cortex. ○ Hypothalamus (H): Regulates autonomic nervous functions and neuroendocrine control (e.g., hunger, thirst, body temperature). Basal Ganglia & Internal Capsule Roles: ○ Involved in eye movement, motivation, and working memory. Internal Capsule: Contains fibers that interconnect the cerebral cortex with the thalamus and basal ganglia. Diencephalon Thalamus: Processes and relays sensory information to the cortex, acting as a sensory gatekeeper. Hypothalamus: Controls autonomic functions and neuroendocrine activities like hunger, thirst, and temperature regulation. Pineal Gland (Epithalamus): An endocrine gland that produces melatonin, regulating sleep-wake cycles. Brainstem Midbrain: Part of the brainstem involved in visual and auditory processing. Hindbrain: ○ Pons ○ Medulla  ○ Cranial Nerves: The brainstem is the attachment point for most cranial nerves, responsible for reflexes and sensory/motor functions. Long Tract Functions: ○ Ascending Reticular Activating System: Responsible for maintaining consciousness and alertness. Cerebellum Longitudinal Divisions: ○ Vermis: Central part of the cerebellum. ○ Cerebellar Hemispheres: Two lateral sections. Lobes: ○ Anterior Lobe ○ Posterior Lobe ○ Flocculonodular Lobe: The oldest part of the cerebellum Functions: ○ Coordination of trunk and limb movements. ○ Eye movements. Meninges of the Brain & Spinal Cord Three Layers: ○ Dura mater: Tough outer layer, fused with the skull's periosteum. ○ Arachnoid mater: Middle layer, attached to the dura mater. ○ Pia mater: Thin, inner layer in direct contact with the CNS. Functions: ○ Provide mechanical support for the CNS. ○ Enclose the cerebrospinal fluid (CSF)-filled subarachnoid space, which cushions the brain and spinal cord. Dura Mater Features: ○ Fused with the skull's inner layer (endosteum). ○ Contains dural septa: Folds that stabilize the brain (e.g., falx cerebri, tentorium cerebelli). ○ Venous sinuses in the dura mater drain blood from the brain. Dura Mater Structure: A tough, outer layer that protects the CNS. Spaces: ○ Epidural space: Located between the cranium and outer dural surface. ○ Subdural space: Found within the innermost dural layer, near the arachnoid.* Venous Sinuses: The dura mater contains large venous sinuses that drain blood from the brain: ○ Superior sagittal sinus ○ Left and right transverse sinuses ○ Straight sinus Arachnoid Mater Structure: A thin, avascular membrane directly in contact with the dura mater. Arachnoid Trabecula: Small strands of collagenous connective tissue within the subarachnoid space, giving the arachnoid its spider-web-like appearance. Arachnoid Villi: Protrusions into the venous sinuses that allow the reabsorption of cerebrospinal fluid (CSF) back into the venous system. Subarachnoid Cisterns Definition: Large pockets of the subarachnoid space that are filled with CSF. Major cisterns: 1. Interpeduncular cistern 2. Pontine cistern 3. Quadrigeminal cistern 4. Cisterna magna Pia Mater Structure: A thin, delicate layer in direct contact with the surface of the CNS. Connections: It is in contact with the arachnoid trabecula on the other side. Vascularization: Surrounds cerebral arteries and veins before they enter or exit the brain. Perivascular Space: The space around blood vessels within the pia mater. Meninges of the Spinal Cord The spinal cord has the same three meninges as the brain, with a few key differences: 1. Epidural space: Exists between the vertebral periosteum and dura mater. 2. Pia mater: Forms longitudinal denticulate ligaments that anchor the spinal cord. 3. Lumbar cistern: A large subarachnoid space at the caudal end of the spinal cord, filled with CSF. Lecture 5 Lecture Notes: Ventricular System and CSF Flow Learning Outcomes: By the end of this lecture, students should be able to: Describe the flow of CSF (Cerebrospinal Fluid) through the ventricular system. Explain the role of the choroid plexus in CSF production and its significance in the blood-brain barrier. Draw and label the Circle of Willis and identify its component arteries. Name the major arteries that supply the cerebrum and cerebellum. Describe the three components of the blood-brain barrier. Ventricular System Embryology Central Canal (Spinal Cord) Ventricular System: ○ Lateral Ventricles (2): Paired, C-shaped structures consisting of 5 parts: frontal horn, occipital horn, temporal horn, body, and atrium. ○ Interventricular Foramen (IV Foramen): Connects the lateral ventricles with the third ventricle. ○ Third Ventricle: Located between and bordered by the thalamus and hypothalamus. ○ Aqueduct (of Sylvius): Connects the third ventricle to the fourth ventricle. ○ Fourth Ventricle: Located in the hindbrain, the space between the cerebellum, pons, and medulla. It communicates with the subarachnoid space via three apertures (recesses). CSF Ventricular Flow Choroid Plexus: ○ Produces CSF (Cerebrospinal Fluid). ○ Lines the lateral ventricles, passes through the interventricular foramen (IV-foramen), and forms the roof of the third ventricle. ○ Exists as a separate strand in the fourth ventricle. ○ It is a component of the blood-brain barrier. Flow Path of CSF: ○ CSF is produced by the choroid plexus.  ○ Flows through the lateral ventricles, passes through the interventricular foramen into the third ventricle, and then through the Aqueduct of Sylvius into the fourth ventricle. ○ From the fourth ventricle, CSF flows into the subarachnoid space via three apertures and is eventually drained back into circulation. Choroid Plexus Overview Primary Function: ○ The choroid plexus is responsible for producing Cerebrospinal Fluid (CSF). Location: ○ Lines the lateral ventricles. ○ Passes through the interventricular foramen (IV-foramen). ○ Forms the roof of the third ventricle. ○ Exists as a separate strand in the fourth ventricle. Role in Blood-Brain Barrier: ○ It is a component of the blood-brain barrier, which regulates the passage of substances from the blood into the brain. Structure of the Choroid Plexus (Damkier et al., 2013) Specialized Area: ○ Composed of ependymal cells and pia mater, which are in direct contact. ○ Ependymal cells in the choroid plexus are specialized, forming choroid epithelium. Tight Junctions: ○ The apical surface of the choroid plexus epithelium has tight junctions that limit the passage of substances, contributing to the blood-brain barrier. Increased Surface Area: ○ The surface area of the choroid plexus is significantly increased by folding.  ○ Total surface area exceeds 200 cm², enhancing its capacity for CSF production. CSF Production Rate Rate of Formation: ○ CSF is produced at a rate of approximately 350 μL/minute. ○ This amounts to about 500 mL/day, which remains relatively constant Hydrocephalus Definition: ○ "Water on the brain" - a condition characterized by an abnormal accumulation of Cerebrospinal Fluid (CSF). ○ CSF is constantly produced, but in hydrocephalus, the balance of production and drainage is disrupted. Causes: ○ Excess CSF production ○ Blockage of CSF circulation ○ Deficient CSF reabsorption Effects: ○ Enlargement of ventricles, leading to compression of brain tissue. Symptoms: ○ Headache, vomiting, nausea, papilledema (optic disc swelling), sleepiness, coma. ○ In infants, it can cause bulging of the cranium due to the soft, flexible skull. Treatments: ○ Placement of a shunt to drain excess CSF. Case Example:  ○ A young child with aqueductal stenosis (narrowing of the aqueduct) caused by a midbrain tumor would experience ventricular enlargement in the lateral and third ventricles, as these are affected by the blocked flow of CSF from the third to the fourth ventricle. Brain Circulation Neuronal Energy and Oxygen Needs: ○ Neurons cannot store energy or oxygen, relying on a constant blood supply. ○ The brain uses 15% of cardiac output and consumes 25% of the body's oxygen. ○ A lack of blood supply (perfusion) for just 10 seconds leads to loss of consciousness. Arterial Blood Supply of the Brain Internal Carotid Arteries (ICA): ○ Branches of the common carotid arteries. ○ Bifurcate into: Middle Cerebral Arteries (MCA): Supplies most of the cerebrum. Anterior Cerebral Arteries (ACA): Also supply the cerebrum. Vertebral Arteries: ○ Branches of the subclavian arteries. ○ Fuse at the pontomedullary junction to form the basilar artery. ○ Branches form: Posterior Cerebral Arteries (PCA): Supply parts of the cerebrum, brainstem, and cerebellum. Multiple cerebellar arteries: Supply the cerebellum. Circle of Willis The Circle of Willis provides a critical connection between the internal carotid and vertebral-basilar arterial systems. ○ Posterior Communicating Artery: Connects ICA to PCA. ○ Anterior Communicating Artery: Connects ACA branches. Function: Normally, little blood moves through the communicating arteries, but they provide a compensatory route if an occlusion occurs. Perfusion of distal tissue is possible if a major vessel is occluded, especially when the occlusion develops gradually. Key Arteries in the Circle of Willis: ACA (Anterior Cerebral Artery) MCA (Middle Cerebral Artery) ICA (Internal Carotid Artery) PCA (Posterior Cerebral Artery) Lecture Notes: Cerebral Arteries Medial Surface Blood Supply Anterior Cerebral Artery (ACA): ○ Supplies the medial surface of the: Frontal cortex Parietal cortex Corpus callosum Posterior Cerebral Artery (PCA): ○ Supplies the temporal cortex and parts of the occipital cortex. Lateral Surface Blood Supply Middle Cerebral Artery (MCA):  ○ Receives 60-80% of the blood flow from the internal carotid artery (ICA). ○ Upper Division: Supplies the frontal and parietal cortices. ○ Lower Division: Supplies the temporal and occipital cortices. Deep Brain Structures Anterior Choroidal Artery (AChA): ○ Branch of the internal carotid artery (ICA). ○ Blood supply to: Optic tract Choroid plexus of the inferior lateral ventricle Thalamus and hippocampus Perforating (Ganglionic) Branches: ○ Small branches of the Anterior Cerebral Artery (ACA), Middle Cerebral Artery (MCA), or Posterior Cerebral Artery (PCA). ○ Supply blood to: Basal ganglia Internal capsule Diencephalon ○ These branches are often compromised during a stroke. Posterior Choroidal Arteries (PChA): ○ Branches of the Posterior Cerebral Artery (PCA). ○ Supply the choroid plexus of the lateral and fourth ventricles. Blood Supply to Hindbrain Midbrain: ○ Supplied by the Posterior Cerebral Artery (PCA). Pons: ○ Supplied by: Anterior Inferior Cerebellar Artery (AICA) Superior Cerebellar Artery (SCA) Pontine arteries Medulla: ○ Supplied by: Posterior Inferior Cerebellar Artery (PICA) Anterior and Posterior Spinal Arteries Cerebellum: ○ Supplied by three cerebellar arteries: AICA PICA SCA Venous Return and Drainage Two Sets of Veins: ○ Superficial Veins: Located on the surface of cerebral hemispheres. Drain into the superior sagittal sinus. ○ Deep Veins: Drain structures in the walls of the ventricles. Converge into internal cerebral veins and drain into the straight sinus. Venous Drainage Pathway: ○ Sagittal and straight sinuses drain into the transverse sinuses. ○ The transverse sinuses drain into the sigmoid sinus, which then drains into the internal jugular vein. ○ Vascular problems in veins are less common than in arteries. Regulation of Blood Flow Normal Blood Flow: 1. ~55 mL/100g brain per minute. Three Major Mechanisms of Regulation: 1. Autoregulation: Blood vessels constrict or relax to maintain constant flow. 2. Local Responses: Example: Glutamate release from neurons binds to receptors on astrocytes, leading to the release of vasodilators, which locally increase blood flow. 3. Autonomic Control: Least important in regulating blood flow but may play a role in long-term adaptations, such as in response to stress. Angiography A diagnostic technique involving the injection of a radiopaque dye into an artery followed by radiographic imaging every 1-2 seconds. Used for identifying vascular pathologies like aneurysms. Aneurysms Definition: ○ Balloon-like swellings of arterial walls, often forming near arterial branch points. Consequences: ○ Compression of brain tissue.  ○ Rupture leading to a subarachnoid hemorrhage. Cerebrovascular Accidents (Stroke) Most common cause of neurological deficits. Caused by a reduction in blood flow, leading to neuronal malfunction or death. Types of Stroke: ○ Ischemic Stroke: Sudden blockage of blood flow. Early treatment can limit permanent damage. ○ Transient Ischemic Attack (TIA): A "mini-stroke" with temporary symptoms. ○ Hemorrhagic Stroke: Arterial rupture, often in small perforating arteries. Symptoms: ○ Vary based on the brain regions affected. Blood-Brain Barrier (BBB) Function: ○ Prevents diffusion of substances into the subarachnoid space from outside the Central Nervous System (CNS). ○ Regulates the composition of Cerebrospinal Fluid (CSF) and controls the flow of components between CSF and plasma. ○ Separates the extracellular space of the CNS from the rest of the body's extracellular space, maintaining a stable environment for the brain. Circumventricular Organs (CVOs) Characteristics: ○ Locations where the cerebral capillaries are fenestrated, allowing relatively free communication between blood and brain tissue. ○ Found around the third and fourth ventricles. Sensory Circumventricular Organs: Area Postrema: ○ Monitors blood for toxins and induces vomiting when necessary. Vascular Organ of the Lamina Terminalis (OVLT): ○ Plays a role in the regulation of fluid balance. Subfornical Organ: ○ Involved in various regulatory functions, including fluid homeostasis and cardiovascular regulation. Secretory Circumventricular Organs: Median Eminence of Hypothalamus & Posterior Pituitary (Neuropophysis): ○ Involved in neuroendocrine regulation, controlling the release of hormones. Pineal Gland: ○ Responsible for the secretion of melatonin, which regulates circadian rhythms. Location of CVOs: Found in the sensory and secretory regions around the third and fourth ventricles of the brain Lecture 6 Learning Outcomes By the end of the lecture, students will be able to: Describe the morphology and functional organization of the spinal cord. Identify and describe the three major ascending and descending tracts. Explain the consequences of a given spinal cord injury. Nervous System Wiring Principles Afferents & Efferents Primary Sensory Afferents: ○ Responsible for receiving information about sensory inputs (e.g., touch, position). ○ Cell body located in sensory ganglia (e.g., dorsal root ganglion). ○ Composed of: Receptive ending Cell body Central terminals (axon terminal) — all on the same side of the body (ipsilateral). Lower Motor Efferent Neurons: ○ Cell body located within the CNS (e.g., in the ventral horn). ○ Axons travel through the periphery and innervate ipsilateral muscle fibers. Somatosensory (Afferent) Information Somatosensory inputs are involved in three information streams: 1. Local reflexes 2. To the cerebral cortex 3. To the cerebellum Pathways to the cerebral cortex cross the midline before reaching the thalamus, leading to processing in the opposite cerebral hemisphere (contralateral). The somatosensory cortex contains a distorted map of the body, known as the homunculus, with greater emphasis on areas like the fingertips and lips. Motor (Efferent) Information Upper Motor Neurons (from the cerebrum) influence the activity of Lower Motor Neurons (LMN). A distorted body map is also observed in the motor cortex, with emphasis on the face (facial expressions) and hands. Corticospinal Tract: ○ Upper motor neurons cross the midline between the cerebral cortex and limbs, influencing contralateral muscle activity. ○ The tract is named based on its origin (“cortico”) and termination (“spinal”), thus termed “corticospinal” as it originates in the motor cortex to synapse on LMN in the spinal cord. Somatotopic Maps (Homunculus) Represents the organization of motor and sensory areas in the brain. Spinal Cord Segmentation Corticospinal Tract: ○ Extends from the brainstem to vertebral level L1/L2. ○ Ends at the conus medullaris. Segments: ○ Cervical: 8 pairs ○ Thoracic: 12 pairs ○ Lumbar: 5 pairs ○ Sacral: 5 pairs ○ Coccygeal: 1 pair Each spinal segment produces a bilateral pair of spinal nerves. Cauda Equina & Filum Terminale Cauda Equina: ○ Also known as “horse’s tail”. ○ A collection of nerve roots from L3 to S5 below the conus medullaris. Filum Terminale: ○ A fibrous tissue that connects the conus medullaris to the coccyx. ○ Composed of pia mater. Ventricular Ligaments - keep the spinal cord in place horizontally Spinal Cord Function Houses all lower motor neurons. Receives the majority of sensory information. Major pathways include: ○ Ascending Sensory Pathways (carry sensory information to the brain) ○ Descending Motor Pathways (carry motor commands from the brain) ○ Reflex Arcs (mediates reflex actions) Functional areas are supplied by spinal segments known as dermatomes. Dermatomes During development, nearby mesoderm segments form somites. Spinal segments maintain connectivity with nearby somites. Somites differentiate into various structures including cartilage, muscle, bone, and skin. Spinal Enlargements Cervical Enlargement (C5 – T1): ○ Necessary for innervating the arms. Lumbosacral Enlargement (L1 – S2): ○ Necessary for innervating the legs. Anterior (Ventral) Horn: (grey matter- efferet) ○ Contains lower motor neurons. Increased white matter -afferet in higher spinal cord levels due to more sensory/motor information passing through (known as funiculi). Spinal Cord Organization Central H-shaped grey matter is surrounded by white matter. Ventral (Anterior) Horn: ○ Ventral rootlets exit and coalesce to form the ventral root. Dorsal (Posterior) Horn: ○ Contains projections from dorsal root ganglion (cell bodies), which divide into dorsal rootlets entering the cord. Spinal Nerves: ○ Formed by the coalescence of ventral and dorsal roots from a given spinal segment. White Matter - Sulci Dorsal Median Sulcus. Dorsal Intermediate Sulcus: ○ Present in the cervical and upper thoracic regions. ○ Divides the dorsal columns into: Fasciculus Gracilis (medial) - carries information from the lower body. Fasciculus Cuneatus (lateral) - carries information from the upper body.  Dorsolateral Sulcus: ○ Entry point for the dorsal roots of spinal nerves into the spinal cord. Ventrolateral Sulcus: ○ Exit point for the ventral roots of spinal nerves from the spinal cord. Ventral Medial Fissure: ○ A deep fissure on the ventral surface of the spinal cord. ○ Location of the anterior spinal artery, which supplies blood to the anterior portion of the spinal cord. White Matter – Funiculi & Fasciculi Funiculi: Regional divisions of spinal cord white matter containing ascending and descending nerve tracts. ○ Dorsal Funiculus: Gracile Fasciculus: Dorsomedial; conveys sensory information from the lower body. Cuneate Fasciculus: Dorsolateral; conveys sensory information from the upper body. ○ Lateral Funiculus: Contains mixed ascending and descending tracts. ○ Ventral Funiculus: Primarily contains descending motor pathways. Gray Matter Organization Posterior (Dorsal) Horn (PH): ○ Responsible for sensory processing. ○ Contains: Lissauer’s Tract: Entry point for some dorsal root ganglion (DRG) fibers. Substantia Gelatinosa: Superficial zone of the PH involved in pain modulation. Intermediate Gray (IG): ○ Contains interneurons and tract cells, along with some autonomic motor neurons (level dependent). Anterior (Ventral) Horn (AH):  ○ Contains motor neurons that innervate muscles. Rexed Laminae Gray matter can be divided by cell type and function into Rexed laminae (I – X): ○ Dorsal Horn (I-VI): Involved in sensory processing. ○ Intermediate Gray (VII): Contains interneurons and autonomic neurons. ○ Ventral Horn (VIII-IX): Contains motor neuron pools. ○ Central Canal (X): Contains cerebrospinal fluid. Organization of Dorsal Horn Sensory Pathways: ○ Medial Stream: Composed of large, myelinated fibers responsible for touch and position. ○ Lateral Stream: Comprised of smaller fibers responsible for pain and temperature sensations. Organization of Ventral Horn Muscle Function Supply: ○ Medial Column: Supplies muscles of the trunk. ○ Midregion Column: Supplies proximal muscles of the limbs (arms). ○ Lateral Column: Supplies distal muscles of the limbs (legs). ○ Extensors: Located anteriorly to flexors within the column organization. Spinal Tracts Definition: ○ Tracts are physiologically distinct pathways in the spinal cord, each responsible for carrying specific types of sensory or motor information (e.g., pain vs. proprioception). Characteristics: ○ Most tracts consist of 2 or 3 neurons.  ○ Each tract has a consistent location at all spinal cord levels. ○ Neurons in these tracts usually decussate (cross over to the contralateral side) at some point in their pathway. Ascending Tract Neurons 1st Order Neuron (Primary Sensory Afferent): ○ The neuron in contact with the sensory receptor or containing the receptive field. ○ Location: Cell body is always in the dorsal root ganglia. 2nd Order Neuron: ○ A projection neuron with its cell body located in the spinal cord or brainstem. ○ Function: Receives sensory information from the primary afferent and projects to either the contralateral thalamus or ipsilateral cerebellum. 3rd Order Neuron: ○ A projection neuron with its cell body located in the thalamic nuclei. ○ Function: Axon projects to the somatosensory cortex (post-central gyrus). Posterior (Dorsal) Column-Medial Lemniscal (DCML) Pathway Function: Primarily carries touch and positional information. Primary Afferents: ○ Composed of large diameter alpha fibers. ○ The posterior column is divided at cervical/thoracic levels into: Fasciculus Gracilis (FG): Carries information from the lower body. Fasciculus Cuneatus (FC): Carries information from the upper body.  Synapse Locations: ○ Primary afferents synapse in nucleus gracilis or nucleus cuneatus in the caudal medulla. Secondary Afferents: ○ Secondary axons decussate (cross) in the medulla and form the medial lemniscus. ○ Synapse in the ventral posterolateral (VPL) nucleus of the thalamus. Tertiary Afferents: ○ Project to the somatosensory cortex that is ipsilateral to the thalamus. ○ Somatotopic organization is maintained throughout the pathway. Spinothalamic Pathway Function: Primarily carries information about pain and temperature. Primary Afferents: ○ Composed of small diameter C and delta fibers. ○ Synapse in the ipsilateral dorsal (posterior) horn. Secondary Afferents: ○ Decussate at all levels of the spinal cord and travel through the lateral funiculus. ○ Synapse in the contralateral VPL. Tertiary Afferents: ○ Project to the somatosensory cortex and other cortical regions. Other Sensory Tracts Cerebellar Tracts: ○ Role: Compare actual movements with intended movements, correcting as needed. ○ Requires proprioceptive information from the spinal cord. ○ Two Main Pathways: Spinocerebellar: Information about the legs. Cuneocerebellar: Information about the arms. ○ Both pathways convey ipsilateral information. Descending Tracts Function: Influence the activity of lower motor neurons. Two Neuron Chain: ○ Upper Motor Neuron (UMN):  Cell body located within the motor cortex (precentral gyrus). ○ Lower Motor Neuron (LMN): Cell body located in the spinal cord; axons project to target organ/muscle. Known as the final common pathway of the motor system. Involves both somatic (voluntary) and autonomic (involuntary) control. Lateral Corticospinal Tract Upper Motor Neurons (UMN): ○ Cell bodies located in the precentral gyrus and surrounding tissues. ○ Bypass the thalamus via internal capsule and cerebral peduncles. ○ Decussate in the pyramids (pyramidal decussation). ○ Travel through the lateral funiculus to synapse on contralateral LMN. Lower Motor Neurons (LMN): ○ Cell body located in the ventral horn of the spinal cord. ○ Fibers project to ipsilateral muscle. Other Descending Pathways (Extra-Pyramidal) Reticulospinal Tract: ○ Two branches: pontine and medullary. ○ Involved in locomotion and posture control. Tectospinal (Olivospinal) Tract: ○ Responsible for the orientation of the head towards sources of visual or auditory stimuli. Vestibulospinal Tract: ○ Maintains center of gravity and posture. Raphespinal (Rubrospinal) Tract: ○ Involved in pain modulation. Lecture 7 Descending Tracts Descending pathways: Influence the activity of lower motor neurons (LMNs). Two neuron chain: ○ Upper motor neuron (UMN): Cell body within the motor cortex (precentral gyrus), responsible for descending inhibition onto LMNs.  ○ Lower motor neuron (LMN): Cell body in the spinal cord; axons project to target organ/muscle (final common pathway of the motor system). Spinal Cord Damage Symptoms depend on the region affected: ○ Spinal cord transection or UMN disease: Initial spinal shock: Flaccid paralysis & areflexia. Followed by hyperreflexia (e.g., Babinski's sign: dorsiflexion of big toe and fanning of others in response to stimulus along the foot). ○ Lower motor neuron (LMN) disease: Flaccid paralysis, areflexia, and muscle atrophy (wasting due to lack of use). Spinal Cord Segments & Lesion Consequences C1-C5: UMN signs in all four limbs. C6-T2: UMN signs in legs, LMN signs in arms. T3-L3: UMN signs in legs, normal arms. L4-S2: LMN signs in legs, normal arms. UMN “sign” = hyperreflexia LMN “sign” = areflexia, muscle atrophy, paralysis *To test if unilateral or bilateral damage, test PAIN on R + L sides Cranial Nerve Classification Sensory (Afferent): 1. General somatic: Pain, temperature, touch. 2. General visceral/autonomic: Parasympathetic functions. 3. Special sensory: Taste, balance, hearing. Motor (Efferent): 1. General somatic: Muscles of orbit & tongue. 2. General visceral/autonomic: Parasympathetic functions. 3. Special visceral/brachial: Muscles of face, jaw, palate, larynx, pharynx. Cranial Nerve Mnemonics 1. I - Olfactory (Sensory) 2. II - Optic (Sensory) 3. III - Oculomotor (Motor, Autonomic) 4. IV - Trochlear (Motor)  5. V - Trigeminal (Both) 6. VI - Abducens (Motor) 7. VII - Facial (Both, Autonomic) 8. VIII - Vestibulocochlear (Sensory) 9. IX - Glossopharyngeal (Both, Autonomic) 10. X - Vagus (Both, Autonomic) 11. XI - Accessory (Motor) 12. XII - Hypoglossal (Motor) On Occasion, Our Trusty Truck Acts Funny, Very Good Van Always Hums Sure, She Makes My Body Melt, But Shes Barely Bothered, Most Mornings 3,7,9,10 and autonomic 5,7,9,10 and both 3,4,6,11,12 motor Mnemonic: "On Old Olympus' Towering Top, A Fine Vet Gladly Viewed A Horse." "Some Say Marry Money, But My Brother Says Big Brains Matter More." Cranial Nerve Functions 1. Olfactory (I): Smell. 2. Optic (II): Vision. 3. Oculomotor (III): Eye movements, pupil constriction, lens accommodation. 4. Trochlear (IV): Eye movements (superior oblique muscle). 5. Trigeminal (V): Facial sensation, chewing. 6. Abducens (VI): Eye movements (lateral rectus muscle). 7. Facial (VII): Facial expression, taste. 8. Vestibulocochlear (VIII): Hearing, balance. 9. Glossopharyngeal (IX): Taste, swallowing. 10. Vagus (X): Senses viscera, speech, swallowing. 11. Accessory (XI): Head and shoulder movements. 12. Hypoglossal (XII): Tongue movement. Cranial Nerve Attachments  Olfactory (I): Olfactory bulb. Optic (II): Optic chiasm. Oculomotor (III): Rostral midbrain (ventral). Trochlear (IV): Midbrain/pons junction (dorsal). Trigeminal (V): Pons (lateral). Abducens (VI): Pontomedullary junction (ventral). Facial (VII): Pontomedullary junction (ventrolateral). Vestibulocochlear (VIII): Pontomedullary junction (ventrolateral). Glossopharyngeal (IX): Rostral medulla (lateral). Vagus (X): Rostral medulla (lateral). Accessory (XI): Cervical spinal cord (lateral). Hypoglossal (XII): Rostral medulla (ventrolateral). Brainstem Cranial Nerve Nuclei Notes Location of Brainstem Nuclei: ○ Brainstem nuclei are organized in predictable areas, similar to the spinal cord. ○ Sensory nuclei are positioned more dorsally back. ○ Motor nuclei are located more ventrally front. ○ Visceral nuclei (those related to internal organ control) are closer to the sulcus limitans (a dividing line between sensory and motor nuclei). Cranial Nerve Nuclei and Function: ○ Each nucleus is typically associated with one or more cranial nerves. ○ Nerves carrying both sensory and motor information will have more than one nucleus. Example: Vagus nerve (X) has both sensory and motor components. ○ Most cranial nerve nuclei supply ipsilateral (same side) nerves, meaning they innervate the same side of the body as their location in the brainstem. Exception: The Trochlear nerve (IV) crosses to innervate the contralateral (opposite side) superior oblique muscle of the eye. Sensory Nerves Olfactory (I): Smell. Optic (II): Vision. Vestibulocochlear (VIII): ○ Vestibular: Balance/equilibrium. ○ Cochlear: Hearing. Olfactory Nerve (CN I) Originates in the olfactory epithelium of the nasal cavity. Contains bipolar receptor cells forming CN I. Unmyelinated axons, group into small bundles—> olfactory bulb Projects directly to the olfactory bulb (an outgrowth of the telencephalon). Olfactory receptors regenerate throughout life. Olfactory Tract Notes Olfactory Tract Projections: ○ Fibers from the olfactory bulb project to several regions: Primary olfactory cortex (piriform and periamygdaloid cortices) in the temporal lobe. —> associated with smell and memory Amygdala (involved in emotion and memory). Olfactory tubercle. The thalamus plays a role in sending projections from the piriform cortex to the olfactory association cortex (orbitofrontal cortex), which combines smell with taste (gustatory information).---> associated with not being able to taste food when you can’t smell Deficits in Olfaction: ○ Conductive Anosmia: Loss of smell due to obstruction or damage to the olfactory receptors or nasal passages. ○ Sensorineural Anosmia: Loss of smell due to nerve damage or brain injury. Optic Nerve (CN II) Notes Retina Structure: ○ The retina converts light into action potentials through three types of cells: 1. Photoreceptors: Includes rods (for low light) and cones (for color vision). 2. Bipolar cells: Relay signals from photoreceptors to ganglion cells. 3. Ganglion cells: Their axons form the optic nerve. Optic Chiasm & Optic Tract Notes Optic Chiasm: ○ The optic nerves undergo partial decussation (crossing over) at the optic chiasm.  ○ Nasal retinal fibers cross to the opposite side, while temporal fibers remain uncrossed. Optic Tract: ○ After crossing, the optic fibers travel through the optic tract to the lateral geniculate nucleus (LGN) of the thalamus. ○ Optic radiation projects from the LGN to the ipsilateral primary visual cortex located in the calcarine sulcus. Visual System Damage Notes 1. Optic Nerve Damage: ○ Affects vision in the ipsilateral eye. 2. Optic Chiasm Damage: ○ Affects the crossing fibers, leading to loss of vision in half of the visual field in both eyes (e.g., loss of the left field in the left eye and the right field in the right eye). 3. Optic Tract Damage: ○ Damage to the right optic tract affects the left visual field of both eyes. Vestibulocochlear Nerve (CN VIII) Notes Function: Responsible for hearing and balance/equilibrium. Two Branches: 1. Vestibular Branch: Conveys information related to proprioception (sense of body position) and head position. Crucial for maintaining balance and coordinating movements. 2. Cochlear Branch: Responsible for hearing. Transmits auditory signals from the cochlea in the inner ear to the brain. Vestibular Nerve (CN VIII) Projects to vestibular nuclei. Some projections go directly to the cerebellum.  Nuclear projections go to: ○ Thalamus ➔ Parietal cortex. ○ Vestibulospinal tracts (medial and lateral). ○ Brainstem nuclei of CN III, IV, VI for the vestibulo-ocular reflex (VOR). Utricle & saccule: Static labyrinth, Linear acceleration Semicircular canals (3): Kinetic labyrinth, Angular acceleration Cochlear Nerve (CN VIII) Transduces sound from the outer ear to the inner ear. Hair cells in the Organ of Corti bend to create auditory signals. ○ Inner hair cells: Principal source of auditory info. ○ Outer hair cells: Control sensitivity. Auditory info is distributed bilaterally in the CNS. Motor Nerves Oculomotor (III), Trochlear (IV), and Abducens (VI): All control eye movements. Accessory (XI): Controls head & shoulder movements. Hypoglossal (XII): Controls tongue movements. Oculomotor Nerve (CN III) Controls the inferior rectus, inferior oblique, medial rectus (ipsilateral), and superior rectus (contralateral) muscles. Edinger-Westphal nucleus: Parasympathetic control of the ciliary and sphincter pupillae muscles. Pupillary light reflex: Assessed for oculomotor nerve dysfunction. Trochlear Nerve (CN IV) Innervates the superior oblique muscle via the trochlear nucleus (contralateral control). Abducens Nerve (CN VI) Innervates the lateral rectus muscle, responsible for eye abduction. Clinical Example Medial strabismus: Loss of lateral gaze.  Inability to retract the globe: Indicates dysfunction in the abducens nerve. Lecture 8 Motor Nerves Overview Motor nerves primarily control voluntary muscle movements. The key motor cranial nerves include: 1. Oculomotor Nerve (CN III): ○ Controls most eye movements and pupil constriction. 2. Trochlear Nerve (CN IV): ○ Controls the superior oblique muscle of the eye, allowing for downward and lateral eye movement. 3. Abducens Nerve (CN VI): ○ Controls lateral eye movement via the lateral rectus muscle. 4. Accessory Nerve (CN XI): ○ Innervates muscles involved in head and shoulder movements. 5. Hypoglossal Nerve (CN XII): ○ Controls tongue movements Accessory Nerve (CN XI) Notes Location: ○ Accessory nucleus is situated in the upper portion of the cervical spinal cord. Innervation: ○ Supplies the ipsilateral sternocleidomastoid (SCM) and trapezius muscles. Function: ○ Shrugging the shoulder. ○ Turning the head to the contralateral side (opposite side). Hypoglossal Nerve (CN XII) Notes Location: ○ The hypoglossal nucleus is found along the midline of the medulla. Innervation: ○ Supplies extrinsic and intrinsic muscles of the tongue. Supranuclear Innervation: ○ Receives corticobulbar fibers from the primary motor cortex for fine movements, such as articulation. ○ Also influenced by the reticular formation, which regulates eating and swallowing. Hypoglossal Nerve Damage 1. Supranuclear Damage: ○ Causes transient weakness of the contralateral muscle. ○ The tongue deviates away from the side of damage due to crossed projections. 2. Nuclear or Nerve Damage: ○ Results in weakness and atrophy of the ipsilateral muscle. ○ The tongue deviates toward the side of damage. Mixed Cranial Nerves Overview Mixed cranial nerves carry both sensory and motor functions: 1. Trigeminal Nerve (CN V): ○ Functions in facial sensations and chewing. 2. Facial Nerve (CN VII): ○ Controls facial expressions and taste. 3. Glossopharyngeal Nerve (CN IX): ○ Involved in taste and swallowing. 4. Vagus Nerve (CN X): ○ The principal parasympathetic nerve, involved in taste, swallowing, and speaking.$$$ Trigeminal Nerve (CN V) Notes Overview: ○ Function: Very large sensory territory, including:  Skin of the face Mucous membranes Teeth Dura mater Intracranial blood vessels ○ Motor Innervation: Muscles of mastication (chewing) Tensor tympani Tensor palati Mylohyoid Digastric muscle Trigeminal Nuclei - Sensory 1. Mesencephalic Nuclei: ○ Only CNS nucleus containing unipolar sensory neurons. ○ Peripheral process extends to the face; central process connects to the supratrigeminal nucleus (motor). 2. Pontine (Principal) Nuclei: ○ Processes tactile information from the face and oronasal cavity. 3. Spinal Nucleus: ○ Receives sensory afferents from the mouth. ○ Processes nociceptive (pain) and thermal information. Facial Nerve (CN VII) Notes Overview: ○ Motor Innervation: Muscles involved in facial expressions. Stapedius muscle in the middle ear. ○ Parasympathetic Outflow: To secretory glands in the eyes, nose, and mouth. ○ Sensory Input: From the tongue and palate (gustatory). Facial Nerve - Main Facial Nerve Facial Motor Nucleus: ○ Provides motor supply for facial muscles.  ○ Nerve loops around the abducens nucleus before exiting the brainstem. Supranuclear Innervation: ○ All cell bodies receive corticobulbar innervation from the contralateral motor cortex. ○ Muscles of the upper face also receive ipsilateral innervation. ○ Functions involve paired activities (e.g., wrinkling forehead). Facial Nerve Lesions Supranuclear Lesion: ○ Causes contralateral motor weakness of the lower face. Nuclear Lesion: ○ Results in complete facial (and abducens) paralysis on the side of the lesion. Nerve Lesion (e.g., Bell’s palsy): ○ Complete facial paralysis on the side of the lesion. ○ Symptoms include inability to raise the eyebrow, close the eye, or retract the lip. Glossopharyngeal Nerve (CN IX) Notes Overview: ○ Primarily a sensory nerve, carrying information from the viscera. ○ Somatic Sensation: From the outer ear. ○ Parasympathetic Innervation: To the parotid gland. ○ Motor Innervation: To the stylopharyngeus muscle, aiding in swallowing and speaking. Glossopharyngeal Nuclei - Sensory 1. Solitary Nucleus: ○ Processes visceral sensory input from: Taste buds (posterior third of the tongue) Carotid body Carotid sinus Mucous membranes.  2. Spinal Trigeminal Nucleus: ○ Receives pain information from the pharynx and posterior third of the tongue. ○ Also receives somatic sensory input from the outer ear. Glossopharyngeal Nuclei - Other 1. Inferior Salivary Nucleus: ○ Provides parasympathetic innervation to the parotid gland (salivary gland). 2. Nucleus Ambiguus: ○ Delivers branchial/special visceral efferent innervation to the stylopharyngeus muscle. Vagus Nerve (CN X) Overview Distribution: ○ The vagus nerve is the most widely distributed cranial nerve, earning the name "vagus," which means "wandering." Function: ○ It serves as the primary parasympathetic nerve to the thoracic and abdominal viscera, providing essential sensory and motor functions. Nerve Functions: ○ Sensory Afferents: Carries sensory information from thoracic and abdominal organs. ○ Motor Efferents: Supplies motor innervation to these same organs, enabling visceral reflexes. Vagus Nerve Nuclei 1. Dorsal Motor Nucleus: ○ Contains preganglionic parasympathetic neurons that innervate the viscera of the thorax and abdomen. 2. Nucleus Ambiguus: ○ Provides: Preganglionic parasympathetic innervation to the heart and other thoracic organs. Branchial motor innervation to the larynx and pharynx, which is crucial for the gag reflex. 3. Solitary Nucleus: ○ Handles:  Special sensory innervation from taste buds located in the epiglottis and esophagus. Visceral sensory information from thoracic and abdominal organs, as well as the larynx and pharynx. 4. Spinal Trigeminal Nucleus: ○ Receives visceral afferents from the larynx, esophagus, and pharynx, contributing to sensory processing. Taste Information via CN VII, IX, and X Taste sensation is conveyed through multiple cranial nerves: ○ Facial Nerve (CN VII): Carries taste from the anterior two-thirds of the tongue. ○ Glossopharyngeal Nerve (CN IX): Carries taste from the posterior one-third of the tongue. ○ Vagus Nerve (CN X): Provides taste sensation from the epiglottis and esophagus. Thalamic Relay Nuclei Interesting Facts Optic Nerve: Projects to the Lateral Geniculate Nucleus (LGN). Vestibulocochlear Nerve: Projects to the Medial Geniculate Nucleus (MGN). Olfaction: Sends signals to the Dorsomedial nucleus of the thalamus and subsequently to the Ventroposteromedial nucleus (VPM), where olfactory information mixes with taste input. Trigeminal, Glossopharyngeal, and Vagus Nerves: All project to the VPM (the vagus nerve also sends projections to the Ventrolateral Nucleus (VPL)). Sensory Pathway Summary  Body Sensation: Relayed through the VPL (spinothalamic and dorsal column-medial lemniscus pathways). Facial Sensation: Processed through the VPM. Smell and Taste: Combined in the VPM and are integrated for gustatory processing. The VPM projects to the inferior salivatory nucleus, facilitating salivation in response to taste stimuli. Lecture 9 Lecture 9: Organization of the Brainstem - Key Notes Learning Outcomes By the end of this lecture, students should be able to: 1. Identify the 6 regions of the brainstem based on key internal and external landmarks. 2. Describe the brainstem nuclei that use dopamine, serotonin, or norepinephrine, and their basic functions. 3. Recognize and label important components in a cross-section of the brainstem. Overview of Brainstem Functions 1. Relay (Conduit) ○ Involves long tracts to and from the spinal cord. 2. Cranial Nerves ○ Serves as the attachment point for most cranial nerves. ○ Contains cranial nerve nuclei. 3. Integrative Functions ○ Regulates cardiovascular and respiratory functions. ○ Manages general visceral sensory and motor functions. ○ Houses the reticular formation, which plays a role in alertness and consciousness. External Anatomy of the Brainstem Dorsal View Medulla ○ Caudal Medulla ○ Rostral Medulla Pons ○ Caudal Pons  ○ Rostral Pons Midbrain ○ Caudal Midbrain ○ Rostral Midbrain Reference Image: Dorsal view (cerebellum removed); important structure: superior cerebellar peduncle (SCP). Ventral View Same divisions as above (medulla, pons, midbrain with rostral and caudal sections). Internal Divisions of the Brainstem 1. Tectum ("Roof") ○ Located posterior to the ventricular space. ○ Notable structures: superior and inferior colliculi in the midbrain. 2. Tegmentum ("Covering") ○ Situated anterior to the ventricular space. ○ Contains the reticular formation, cranial nerves and nuclei, and spinal tracts. 3. Appended Structures ○ Includes cerebral peduncles, basal pons, and pyramids, contributing to motor and sensory pathways. Reticular Formation ("Consciousness") Location: Core tissue throughout the brainstem. Key Functions: ○ Respiratory Control: Regulates breathing patterns.ask ○ Cardiovascular Control: Maintains heart rate and blood pressure. ○ Sleep/Wake Cycles: Managed by the ascending reticular activating system (ARAS), important for arousal and wakefulness. ○ Sensory Modulation: Filters and prioritizes sensory information. ○ Reflex Control: Involved in reflexes such as coughing. Brainstem Nuclei Overview Focus has been on brainstem nuclei with specific connectivity (e.g., spinal tracts and cranial nerve nuclei). Some brainstem nuclei have widespread connectivity, impacting broader brain activities. Key nuclei with distinct small-molecule neurotransmitters: 1. Locus Coeruleus: Noradrenaline 2. Substantia Nigra: Dopamine 3. Ventral Tegmental Area (VTA): Dopamine 4. Raphe Nuclei: Serotonin Detailed Overview of Key Brainstem Nuclei Locus Coeruleus – Noradrenaline Location: Floor of the 4th ventricle in the rostral pons. Projections: Thalamus, hypothalamus, hippocampus, and cerebral cortex (particularly somatosensory areas). Functions: ○ Maintaining attention and vigilance. Substantia Nigra & VTA – Dopamine Substantia Nigra (Compact Part): ○ Location: Rostral midbrain. ○ Projections: Striatum and putamen (nigrostriatal pathway). Ventral Tegmental Area (VTA): ○ Location: Rostral midbrain. ○ Projections: Cerebral cortex and amygdala (mesocortical and mesolimbic pathways). Roles: ○ Involved in movement initiation, motivation, and cognition. Raphe Nuclei – Serotonin Location: A series of nuclei along the midline within the brainstem reticular formation. Projections: All parts of the CNS, with higher density in sensory and limbic cortical regions, cerebellum, brainstem, and spinal cord. Function: ○ Regulates the overall level of arousal. ○ Influences mood, emotion, and sleep through serotonin modulation. Brainstem Cross Sections (Caudal to Rostral) The following colors represent specific functions and structures in brainstem cross-sections: 1. Red: Motor pathways and nuclei 2. Blue: Sensory pathways and nuclei 3. Green: Connections with the cerebellum and reticular formation 4. Purple: Special nuclei (unique functional areas) 5. Black: Other significant landmarks or structures of interest Each color aids in identifying key regions across various levels of the brainstem, moving from the caudal (lower) to the rostral (upper) aspect. Medial Longitudinal Fasciculus (MLF) Location: Extends the full length of the brainstem. Fiber Composition: Varies at different brainstem levels. Key Functions: ○ Eye Movements: Coordinates activity between the oculomotor, trochlear, and abducens nuclei, crucial for synchronized eye movement. ○ Vestibular Compensations: Supports balance adjustments, such as during gait, by integrating vestibular signals. Lecture 10: The Cerebral Cortex - Key Notes Learning Objectives By the end of the lecture, students should be able to: 1. Describe the neocortex's layer structure in detail. 2. Identify the afferent (input) and efferent (output) connections of the neocortex. 3. Associate basic functions with cortical areas based on location or Brodmann area number. Neocortical Lamination (6 Layers) Layer I: Cell-poor, mainly supportive. Layer II: Contains granular cells. Layer III: Contains small pyramidal cells. Layer IV: Contains granular cells Layer V: Large pyramidal cells, critical for motor output. Layer VI: Fusiform (spindle-shaped) pyramidal cells. Note: The thickness of these layers varies based on the function of each cortical area. For example:  Motor Cortex: Thicker in pyramidal cell layers (layers III and V), fewer granule cells, numerous pyrimidal cells. Neocortical Connectivity Afferents (Inputs) Subcortical Sources: ○ Thalamic Relay Nuclei (e.g., VPL(ventral posterolateral)/VPM (ventral posterior medial): Primarily project to middle layers, especially layer IV. ○ Other Thalamic Nuclei (e.g., LGN (lateral geniculate nucleus)/MGN (media geniculate nucleus): Relay sensory information to cortical layers. Corticocortical Connections: Mostly project to layers II and III, Efferents (Outputs) Subcortical Targets: ○ Basal Ganglia, Brainstem & Spinal Cord: Primarily arise from layer V. ○ Thalamic Regulatory Projections: Originate mainly from layer VI. Corticocortical Outputs: Primarily from layer III Cerebral Cortex Efferent Pathways Corticocortical: ○ Commissural Pathways: Use the corpus callosum and anterior commissure to connect to the contraleteral hemisphere. ○ Association Pathways: Short and long projections to ipsilateral hemisphere. Projection Fibers: ○ Subcortical ○ Corticothalamic Association Fibers and Functional Divisions of the Cerebral Cortex - Key Notes Association Fibers Short Association Fibers ("U fibers"): Connect adjacent gyri within the same lobe. Long Association Fibers: Connect different lobes of the brain. ○ Superior Longitudinal Fasciculus (Arcuate Fasciculus) ○ Cingulum Fasciculus  ○ Uncinate Fasciculusv Brodmann’s Areas Overview: ○ Created by German anatomist Korbinian Brodmann (1868-1918). ○ Divided the cerebral cortex into 46 distinct areas based on cellular structure (cytoarchitecture). ○ Areas are similar to the Rexed laminae in the spinal cord. ○ Boundaries between areas are not sharply defined and can vary among individuals. ○ Some areas correlate with specific functional regions of the cortex. Five Lobes of the Cerebrum The cerebrum is divided into five lobes: 1. Frontal 2. Parietal 3. Temporal 4. Occipital Functional Divisions of the Cortex Primary Sensory/Motor Areas Function: Receive sensory information from the outside world or send motor commands to the body. Organization: ○ Topographically organized, with a focus on areas requiring fine motor control. ○ Motor & Somatosensory: Organized as a Homunculus ○ Auditory: Organized by tonal frequency.  ○ Visual: Retinotopic organization (mimics the spatial arrangement of the retina). Unimodal Association Areas Location: Adjacent to primary sensory or motor areas. Function: Enable more complex responses to sensory inputs and are mainly connected to their corresponding primary areas. Multimodal Association Areas Function: Integrate multiple sensory inputs, allowing for complex cognitive functions such as speech, executive functions, and decision-making. Parietal Lobe - Somatosensation Inputs: ○ Thalamus Ventral posterolateral (VPL): Receives medial lemniscus (DCML) input. Ventral posteromedial (VPL/VPM): Receives spinothalamic (AL) input. Primary Somatosensory Area (S1):postcentral gyrus. Secondary Somatosensory Area (S2) Somatosensory Association Cortex: In Brodmann areas 5 & 7; integrates sensory inputs for perception. Occipital Lobe – Vision Input: Lateral geniculate nucleus via optic radiation. Primary Visual Cortex (V1): Brodmann area 17; essential for visual perception. ○ Lesions: Can cause total or near-total loss of visual awareness. Visual Association Cortex (V2-5): Brodmann areas 17, 18, 19, and other areas; processes visual information for interpretation. Temporal Lobe – Hearing Inputs: ○ Medial geniculate nucleus projects to the cortex. Primary Auditory Cortex: Brodmann area 41, organized as a tonotopic map of frequencies. ○ Lesion: Limited impact due to bilateral information travel; may affect sound localization. Secondary Auditory Cortex: Brodmann area 42. Auditory Association Cortex: Brodmann area 22 (with Brodmann areas 44 & 45, also part of Broca’s area). ○ Lesion: Language issues, such as Wernicke's, and difficulty understanding prosody. Frontal Lobe – Motor Cortex Primary Motor Cortex (M1): Brodmann area 4, Premotor Cortex (PMC): Lateral part of Brodmann area 6. Supplementary Motor Area (SMA): Medial part of Brodmann area 6. Output: Contributes to the corticospinal tract Posterior Parietal Cortex (PPC) Location: Positioned posterior to S1. Disorders: ○ Agnosia: "Lack of knowledge" - inability to recognize objects using certain senses (e.g., visual agnosia for faces or movement). ○ Contralateral Neglect: Often occurs with right posterior parietal damage, leading to inattention to the left side. ○ Apraxia: "Lack of action" - inability to perform certain actions despite intact motor function. Prefrontal Cortex (PFC) Location: Frontal lobe, anterior to Brodmann areas 4 & 6 (motor regions). Functions: Executive functions like planning, insight, foresight, and personality regulation. Subdivisions:  ○ Dorsolateral PFC: Connects with the dorsomedial nucleus of the thalamus; involved in working memory. ○ Ventromedial PFC: Connects with limbic structures like the amygdala; damage may lead to impulsive, inappropriate behaviors and emotional instability. Case Study: Phineas Gage Background: Suffered prefrontal cortex damage after a railroad spike injury. Effects: Marked personality changes, including impulsiveness, profanity, impatience, and reduced social restraint, highlighting the PFC's role in personality and behavioral regulation. Lecture 11: Cerebellum Divisions: ○ Longitudinal: Vermis: Central strip of the cerebellum. Cerebellar Hemispheres: Lateral portions. ○ Lobes: Anterior Lobe Posterior Lobes (2  Flocculonodular Lobe Cerebellum Basics Often referred to as the "little brain." Accounts for 10% of total brain mass. Contains as many neurons as the entire rest of the central nervous system combined! Key functions include: ○ Equilibrium: Maintenance of balance. ○ Postural Control: Stabilization of body posture. ○ Coordination of Voluntary Movements: Fine-tuning motor activity. Cerebellar Divisions Primary Fissure: Divides the cerebellum into anterior and posterior lobes. Posterolateral Fissure: Separates the flocculonodular lobe from the rest of the cerebellum. Functional Division of the Cerebellum Divided into functional longitudinal strips that include both the cerebellar cortex and deep internal structures: ○ Vermis:------------------ Spinocerebellum ○ Medial Hemisphere– ○ Lateral Hemisphere: Pontocerebellum ○ Flocculonodular Lobe: Vestibulocerebellum Deep Cerebellar Nuclei Underlying each functional division of the cerebellar cortex are: ○ Fastigial Nucleus ○ Interposed Nucleus ○ Dentate Nucleus Cerebellar Connectivity All parts of the cerebellum use similar basic circuitry. Functional differences arise from variations in connectivity and inputs/outputs. Cerebellar Peduncles Superior Cerebellar Peduncle: Primary output pathway for the cerebellum. Middle Cerebellar Peduncle: Receives inputs from the contralateral cerebral cortex via pontine nuclei. Inferior Cerebellar Peduncle: Contains a mix of afferent and efferent fibers Cerebellar Structure Known as the "Arbor Vitae" (Tree of Life) due to its tree-like appearance. Cortical Surface: Indented with small creases known as folia. Cerebellar Cortex: Composed of three layers:  ○ Molecular Layer: Outer layer with few neurons. ○ Purkinje Cell Layer: Middle layer containing Purkinje cells, which are critical for output. ○ Granular Layer: Inner layer rich in granule cells. Cerebellum: Inputs, Connectivity, and Functions Cerebellar Inputs Two Major Types of Input: ○ Mossy Fibers: Projections from various regions of the brain. Synapse with granule cells. Granule cells extend parallel fibers that synapse with multiple Purkinje cells. ○ Climbing Fibers: Originate from the contralateral inferior olivary nucleus. Synapse directly with Purkinje cells. Parallel & Climbing Fibers Parallel Fibers: ○ Each granule cell generates one or two parallel fibers. ○ One parallel fiber contacts multiple Purkinje cells. ○ Many parallel fibers are needed to activate a Purkinje cell. Climbing Fibers: ○ Each Purkinje cell receives input from a single climbing fiber. ○ A single climbing fiber can form thousands of synaptic connections with a Purkinje cell. Cerebellar Cortex Connectivity Input Mechanisms: ○ Mossy fiber → Granule cell → Parallel fiber → Multiple Purkinje cells. ○ Climbing fiber → Single Purkinje cell. Output Mechanism: ○ Axons of Purkinje cells are the sole output from the cerebellar cortex. ○ They project to deep cerebellar nuclei. Cerebellar Hypoplasia Condition caused by the feline leukopenia virus during gestation. Results in the destruction of Purkinje cells. Deep Nuclei of the Cerebellum Flocculonodular Lobe: Projects to vestibular nuclei. Vermis: Projects to fastigial nucleus. Medial Hemisphere: Projects to interposed nucleus. Lateral Hemisphere: Projects to dentate nucleus. Cerebellar Outputs Each functional zone has specific output pathways: ○ Fastigial Nucleus: Projects to vestibular nuclei and reticular formation. ○ Interposed & Dentate Nuclei: Project to the red nucleus and thalamus, which relay to the contralateral cerebral cortex. The cerebellum primarily influences the ipsilateral side of the body. Cerebellar Functions Lateral Hemispheres: ○ Involved in planning movements. Medial Hemispheres: ○ Adjust limb movements. Vermis: ○ Responsible for postural adjustments. Flocculus & Vermis: ○ Involved in eye movements. Lecture 12: Basal Ganglia Learning Objectives  Major Nuclei: Identify the main nuclei composing the basal ganglia. Connectivity: Describe the connections within the basal ganglia. Pathways: Explain the roles of the direct and indirect pathways. Functions: Attribute basic functions to the basal ganglia. Parkinson’s Disease: Understand basal ganglia involvement in Parkinson’s disease. Overview of Basal Ganglia Definition: A group of nuclei in the basal forebrain and midbrain. Key Functions: Primarily involved in motor control. Major Structures (5): ○ Caudate nucleus ○ Putamen ○ Globus pallidus (external - GPe, internal - GPi) ○ Subthalamic nucleus (STN) ○ Substantia nigra (SN) Additional Groupings: ○ Striatum: Includes caudate, putamen, and nucleus accumbens. ○ Lenticular Nucleus: Composed of putamen and globus pallidus. Fiber Terminology Naming based on origin and destination: ○ Nigrostriatal: From substantica nigra to striatum. ○ Pallidothalamic: From globus pallidus to thalamus. ○ Striopallidal: From striatum to globus pallidus. Afferent Connections of Basal Ganglia Cortex: Corticostriatal fibers (glutamatergic). Thalamus (Intralaminar): Thalamostriatal (glutamatergic). Substantia Nigra (Compact part): Nigrostriatal fibers (dopaminergic). Efferent Connections of Basal Ganglia Globus Pallidus Internal (GPi): Pallidothalamic (GABAergic). Substantia Nigra (Reticular part): Nigrothalamic (GABAergic). Basal Ganglia Circuits and Functions 1. Motor Loop: Manages learned movements. 2. Cognitive Loop: Involved in planning and motor intentions. 3. Limbic Loop: Connects emotion with movement. 4. Oculomotor Loop: Manages voluntary eye movements.  ○ Focus: Motor loop - connects sensorimotor/association cortex → striatum → thalamus → motor cortex & supplementary motor area. ○ Role: Does not initiate voluntary movement but facilitates proper motor responses and inhibits inappropriate actions. Direct Pathway Sequence: ○ Motor cortex excites putamen. ○ Putamen increases inhibition GPi. ○ GPi can no longer inhibit the thalamus causing disinhibition ○ Thalamus excitation of the motor cortex is allowed. Purpose: Promotes movement by disinhibiting the thalamus. Indirect Pathway Sequence: ○ Motor cortex excites putamen. ○ Putamen increases inhibition of GPe. ○ GPe can no longer inhibit the subthalamic nucleus causing disinhibition of STN ○ STN is free to excite GPi. ○ GPi inhibits the thalamus ○ Thalamus cannot excite motor cortex Purpose: Inhibits movement. Balance Between Direct and Indirect Pathways The basal ganglia’s output is a balance between the activation of the direct (movement-promoting) and indirect (movement-inhibiting) pathways. Dopaminergic Modulation: ○ D1 Receptors: Excite neurons in the direct pathway. ○ D2 Receptors: Inhibit neurons in the indirect pathway. Disorders of the Basal Ganglia Hyperkinetic Disorders: ○ Symptoms: Tremors, chorea (rapid, involuntary movements), athetosis (slow, writhing), ballismus (wild flailing). ○ Example: Huntington’s disease. Hypokinetic Disorders: ○ Symptoms: Rigidity, bradykinesia (slow movement), stooped posture, resting tremor. ○ Example: Parkinson’s disease. Dementia: Also linked to basal ganglia dysfunction. Parkinson’s Disease (PD)  Symptoms: Bradykinesia, hypertonia, dyskinesia, tremor, and akinesia. Cause: Degeneration of dopaminergic neurons in the substantia nigra compacta (SNc). LECTURE 13: THE THALAMUS & HYPOTHALAMUS Learning Objectives By the end of today’s lecture, students will be able to: 1. Name the 4 divisions of the diencephalon. 2. Name the divisions of the thalamus and the major nuclei found within each region. 3. Name the major regions and nuclei of the hypothalamus. 4. Describe the functions attributed to the hypothalamus. Diencephalon Comprises 2% of total brain volume. Consists of 4 parts, each containing “thalamus” in the name (Latin for “inner chamber”): ○ Epithalamus Pineal gland: Midline, unpaired structure shaped like a pinecone; secretes melatonin in response to darkness, regulates reproductive cycles and circadian rhythms. Habenula: Plays a role in aversion. ○ Thalamus: Large, egg-shaped nuclear mass, accounts for 80% of the diencephalon. Serves as the gateway to the cortex; all sensory pathways relay through the thalamus and it is involved in basal ganglia, cerebellar, and limbic system circuits. ○ Subthalamus: Contains the rostral portions of the red nucleus and substantia nigra. Includes the subthalamic nucleus and zona incerta (a small area of grey matter between the thalamus and subthalamic nucleus; a continuation of the midbrain reticular formation). ○ Hypothalamus: Contains the mammillary bodies. Thalamus Thalamic Inputs: ○ Specific Input: Conveys accurate information that specific nuclei may pass on to the cerebral cortex (e.g., medial lemniscus to VPL). ○ Regulatory Input: Influences whether information leaves a given nucleus (e.g., input from the cerebral cortex).  Thalamic Divisions: ○ Subdivided into nuclear groups by the internal medullary lamina. Principle Thalamic Nuclei: 1. Anterior: Anterior nucleus (A). 2. Medial: Dorsomedial nucleus (DM). 3. Lateral: ○ Ventral anterior nucleus (VA). ○ Ventrolateral nucleus (VL). ○ Ventroposterolateral nucleus (VPL). ○ Ventroposteromedial nucleus (VPM). ○ Pulvinar nucleus (Pul). ○ Lateral geniculate nucleus (LG) - visual processing. ○ Medial geniculate nucleus (MG) - auditory processing. Other Thalamic Nuclei: Intralaminar Nuclei: Collections of cells within the internal medullary lamina (e.g., centromedian (CM) & parafascicular (PF) nuclei) that project to the cerebral cortex and basal ganglia. Thalamic Reticular Nucleus: ○ Located between the external medullary lamina and internal capsule. ○ Contains no projections to the cerebral cortex; provides regulatory GABAergic projections to other thalamic nuclei. Types of Nuclei 1. Specific or Relay Nucleus ○ Function: Receive specific inputs from subcortical areas and send outputs to the cerebral cortex. ○ Example: Medial geniculate nucleus. 2. Association Nucleus ○ Function: Receive most specific inputs from cortical regions and distribute them to other cortical regions. ○ Example: Dorsomedial nucleus. 3. Non-Specific Nucleus ○ Function: Not specific to any one sensory modality. ○ Example: Intralaminar nuclei. Corona Radiata & Internal Capsule  Corona Radiata ○ A bundle of white fiber tracts that fan out throughout the cerebral cortex. ○ Narrows to pass through the internal capsule on the way to the brainstem and spinal cord.