Neuroanatomy BIOM 3000 NOtes.pdf

What is Neuroanatomy? The study of the anatomy and organization of the central nervous system of animals Radial Symmetry: nerves and axons radiate from a core Bilateral Symmetry: identical structures on the left and right Neuroanatomical Terminology Anterior/Posterior: front/back (aka rostr...

What is Neuroanatomy? The study of the anatomy and organization of the central nervous system of animals Radial Symmetry: nerves and axons radiate from a core Bilateral Symmetry: identical structures on the left and right Neuroanatomical Terminology Anterior/Posterior: front/back (aka rostral/caudal) Medial/Lateral: inside/outside Superior/Inferior: top/bottom (dorsal/ventral) all I I 1 Cells of the Nervous System Neurons Central Nervous System (CNS) Convey information through electrical and Brain and spinal cord chemical signals Neuron Classi cation White Matter: myelinated axons Oldest and longest cells Can be classi ed based Gray Matter: cell bodies & dendrites] Functional unit of behaviour on structure... Limited ability to be replaced Dendrites branch off axon: Glia Unipolar denariaic arbourization Provide a support system for neurons (both Pseudo-unipolar physical and metabolic support) Bipolar Variety of types and functions Dendrites branch off Presences is crucial for neurons cell body: Multipolar i oniyinnpn fhfyfgf.fi on 6projection diff ofAf rootganglion dorsal i sensoryAfferent Neurons are polarized Functional and anatomical polarization Regardless of the type of neuron, signalling occurs in an organized, consistent manner a Visualization of Neurons staff Golgi Staining Silver staining technique for use under light microscopy É g Potassium dichromate & silver nitrate (black precipitates) Stains a limited number of cells at random (don't know why Neuron Filling certain ones stain and others don't) I Via injection of axonal transport Camilo Golgi, Santiago Ramon y Cajal Ex: biotin derivatives, GFP, lucifer yellow, viruses (spider- ◦ Together won in 1906 Nobel Prize in Medicine for their rabies/herpes) etc... work on the structure of the nervous system Targeted lling of neurons of interest Takes advantage of polarity and transport mechanisms Immunochemisty Methods for loading Localization of proteins (antigen) using antibodies to ◦ Micro injection speci c proteins ◦ Whole-cell patch clamping (most common) ◦ Some are speci c for neurons and some are speci c ◦ Electroporation ( + tracer will go to the - neuron) for astrocytes PInaa I ay te oxidase  Glial cells rolesmechanicalsupport metabolicsupport thereis at ratioofglialcellstoneurons am ensembrane Oligodendrocytes Shrink.pe fefhspns a igqeings ftp.tgb1qIIpg My t.gg tgeiignehis.iespsoiseftlinInegna.itfIqnffa Y t 8 atn7o IEaYIee a s tggg.ttgwes.awnguddisseYYees scinateanaiamovementotes isspecializedepenaymaproaucescsf FI g gg iati n choroid p lexusstemcensarebornnere regenastieasesitneonison Cst macrophagephagocytic Brain Gersbloodmakes.se Ion Channels Ionic Equilibrium and Resting Membrane Potential (RMP) Na+/K+ ATPase (Pump) 3 properties: All cells have ionic equilibrium responsible for their RMP, but only Active transport ◦ Ion speci c nerve and muscle cells are 'excitable' Hydrolysis ATP ◦ Open/close in response to How the RMP is established 2 K+ into the cell, 3 Na+ out of the cell certain stimuli ◦ 1. Semi-permeable, selective membrane (for K+ and Cl-), Ion ow during action potential distrusts the ◦ Passive movement of ions impermeable to Na+ ionic equilibria, therefore pump restores down electrochemical ◦ 2. K+ equilibriates based on electro-chemical gradient (Ek) electronegativity gradients across membrane ◦ 3. RMP of most cells is -70mV Water follows Na! During action potential, Types: cells swell, therefore the pump removes ◦ Ligand gated: open in water by pumping out sodium j response to binding of ligand Na+/K+ ATPase pump restores gradient (over (neurotransmitter) long-term ONLY) only required after ◦ Voltage gated: open and i sustained activity after 1000 action close in response to changes potentials in membrane potential (voltage) ◦ Mechanical/stretch gated ◦ *Leak Channels: these channels are always open n Refractory Periods Absolute refractory period ◦ Cell cannot respond to further Action Potentials stimulation Rapid changes in membrane potential of an axon ◦ Inactivation of Na+ channels Propagation begins at the axon hillock Relative refractory period Propagated over long distance utilizing voltage-gated ◦ Cell can respond, but requires ion channels a greater then normal 4 important properties threshold cs't.it excitation ngigfggggf ◦ 1. Threshold Ensure APs only generate/ ◦ 2. All-or-none event propagate in one direction ◦ 3. Conduction without decay ◦ 4. AP is followed by a refractory period (to keep The Synapse Steps in Synaptic Transmission the signals going inrone direction) Specialized junction that allows neurons 1. Production of neurotransmitters to communicate w each other and organs 2. Packing of neurotransmitters TheAxonHillockandThreshold Elements of the synapse 3. Release of neurotransmitters ◦ Presynaptic ending 4. Binding to receptors ◦ Synaptic cleft 5. Termination of neurotransmitter action i ◦ Postsynaptic element ig Synthesis of Neurotransmitters (NTs) Main types: small amines, amino acids or (neuro)peptides Small molecule NTs are made in the axon terminal by enzymes (Ex: acetylcholine, choline acetyl-transferase ChAT) Peptide NTs are made in the cell body and transported to the presynaptic endings ◦ Often made as a larger precursor peptide (Ex: corticotropin releasing factor CRF) p Release of Neurotransmitters Ca2+-mediated secretion Depolarization of presynaptic terminal opens voltage-gated Ca2+ channels p Synaptic vesicles fuse with membrane (exocytosis)  Binding to Receptors Small vesicle NTs: diffuse rapidly across synaptic cleft, rapidly bind to receptors Large vesicle NTs: slower release, more distance receptors, slower response Effects of NTS are determined by the receptors in the postsynaptic membrane Responses can be: ◦ Fast or slow ◦ Excitatory (EPSP) or Inhibitory (IPSP) - depends on channel (Na/K/Cl) activated Termination of Neurotransmitter Action NTs need to be removed quickly so that the postsynaptic membrane can prepare for subsequent release of NT Mechanisms: ◦ Reputable by the presynaptic membrane or neighbouring glial cells (Ex: serotonin, norepinephrine, dopamine) ◦ Enzymatic inactivation (Ex: acetylcholine by acetylcholinesterase AChE) ◦ Uptake by postsynaptic terminal ◦ Diffusion out of synaptic cleft Embryology - Germ Layers Origins of CNS/PNS development Endoderm: gut liver lungs CNS Mesoderm: skeleton, muscle, kidney, heart Induction by mesoderm of the ectoderm to form 'neuroectoderm' -> Neural plate -> neural tube Ectoderm: skin and nervous system (both Neural tube gives rise to the brain and spinal cord (rostral and caudal respectively) CNS and PNS) PNS Diverse sources ◦ Neural crest cells ◦ Neural tube: preganglionic autonomic nerves and motor nerves ◦ Mesoderm: meninges and connective tissue surrounding peripheral nerves CellsofatheetmervousSystem Errors in Neurulation Spine Bi da: incomplete closure of Itf ftp.gyattfnw eeIntg spartotens caudal end of neural tube fm ntentqieaie gnetigtinnkamfeYeenginottneemmo ◦ Range in severity of de cit neuraicreqm.ienytottne Intringenitions Means Ward yygggyp.gg gggdgg t MNMfMEEyyÉÉÉÉ we ÉIÉÉ I r Encephalocele: incomplete closure of rostral end of neural tube egging ◦ Sac-like protrusion of brain & Ii surrounding membranes me Anencephaly: incomplete closure of the rostral end of the neural tube hzrain spinalcordDevelopment Adht ◦ lack of telencephalon (cerebrum) Development RostralNeurath I laga 1 is e ftp.gyggggyehggtegtrea gunna y ans gg caudalNeuralTube a Y me I a É Yard  Cell Proliferation Neuronal Migration Neurogenesis Most neurons produced in VZ migrate radially (in red) Proliferation of neural progenitors ◦ Somal translocation ◦ Ventricular zones (VZ): a transient embryonic ◦ Guided by radial glial cells: guide the cell bodies to layer of tissue containing neural stem cells, their nal functioning place principally radial glial cells, of the CNS Tangential migration (in blue) Synaptogenesis, Myelinogeneiss and Gliogenesis, all ◦ Medial and lateral ganglionic eminence continue after birth ◦ Inhibitory cortical interneurons (short inner neurons) Neural Crest Cells - PNS Development Programmed Cell Death Develop from cells on lateral aspect of 2 important 'regressive events' in brain development neural plate 1. Apoptosis Highly proliferative Neuronal populations lost prenatally Differentiate into a number of neural and ◦ Up to 70% in some cortical areas non-neural tissues ◦ Mechanism for correcting errors? probably Migrate throughout the embryo ◦ Eliminating transient cell populations (marginal zone 2 types: cranial & trunk and subplate) Glial populations lost postnatally ◦ Loss of excess oligodendrocytes during myelination Dorsal Root Ganglion Why you can't remember life as a baby? Provide sensory information from 2. Synaptic Exuberance and Pruning Hippocampal neurogenesis the body Massive production of synaptic connections followed by up Excessive 'retiring' of connections ('plasticity') Synapse with sensory neurons to a 50% loss of them Hippocampus is still growing during childhood within the dorsal horn Largely postnatal, over months or years Mechanisms: neurotrophic support and afferent input Abnormal Neural Crest Cells Nervous System Repair Neurocristopathies: a diverse Wide variety of regenerative class of pathologies involving cells capabilities Autonomic Nervous System derived from the neural crest Leopard gecko, can regenerate 2 neuron system: preganglionic and postganglionic ◦ Waardenburg Syndrome/ functional tail following tail loss Sympathetic Nervous System ('Fight or Flight") Albinism Developing mammals, some can ◦ Preganglionic: Basal plate at thoracic and lumbar level ◦ Neuro bromatosis: all balls regenerate but it is lost overtime ◦ Postganglionic: Neural crest derived neurons with cell bodies are lled with neurons and Adult Mammals, limited repair, PNS is in sympathetic chain ganglia (close to spinal cord) nerves, ectoderm didn't fully better at regenerating then CNS ‣ Exception: Chromaf n cells of adrenal medulla, neural differentiate between skin crest derived and nervous system Parasympathetic Nervous System ('Rest and Digest') ◦ Cleft lip and cleft palate ◦ Preganglionic: basal plate of brain stem and sacral level ◦ Postganglionic: Neural crest derived neurons with cell bodies close to the organs of innervation PNS Repair/ Regeneration Visceral organ sensory and motor function Neurons lost to disease/injury Differ in: don't usually regenerate ◦ Length of pre vs postganglionic neurons Axon transaction ◦ Neurotransmitter at postganglionic cell ◦ Wallerian degeneration ◦ Schwann cell proliferation CNS Repair/Regeneration ◦ Increased RNA Neurons lost to disease/injury generally not replaced synthesis in neuron Adult neurogenesis (ependymal cells) If innervation successful, ◦ Subgranular zone of the hippocampus function is restored ◦ Subventricular zone of the lateral ventricles Axon transection ◦ Wallerian degeneration ◦ Astrocytes and oligodendrocytes actively impede regeneration ◦ Glial scar: reactive astrocytes secrete chondroitin sulfate proteoglycans (CSPGs) which help with joint In the brain the grey matter surrounds the white matter Hemisphere Connectivity Sulcus & Gyrus In the spinal cord the white matter surrounds the grey matter 2 major connective tracts Sulcus (Sulci): I between hemispheres depression or groove Corpus callosum: interconnects ◦ Deep sulci -> most cortical areas ssures Anterior commissure: Gyrus (Gyri): ridge or connection between temporal fold between 2 sulci lobe cortical regions Increase surface area of A frontal section through the cortex/cerebrum mouse because smooth Provide important Armato landmarks Cerebrum: more surface area = more neurons + more glial cells  Lobes of the Cerebrum Sulci Gyri 4 major sulci de ne the 4 major sulci Gyri are named in relation to the boundaries of the cerebral lobes Lateral surface sulci There are 5 lobes... ◦ Central sulcus (of Rolando) Ex: precentral and postcentral mmmm Frontal ◦ Lateral sulcus/Sylvian Fissure: gyrus, surrounds the central ◦ Motor functions -> separates temporal lobe from sulcus precentral gyrus contain rest of the brain Ex: superior, middle and inferior primary motor cortex Medial surface frontal gyrus, near the inferior ◦ Broca's area -> production ◦ Parietoocciptal sulcus and superior frontal sulcus in a of written & spoken language Parietal ◦ Cingulate sulcus Names of other sulci are derived from Correspond to functional areas ◦ Somatosensory information their relative location -> postcentral gyrus The Limbic Lobe (System) contains primary Internal Cerebral Anatomy Basal Ganglia & Internal Capsule somatosensory cortex Limbic System nuclei Roles in eye movement, motivation & Occipital ◦ Amygdala (Am) working memory ◦ Vision -> contains primary ◦ Hippocampus (HC): is Internal capsule: bres interconnecting visual & association cortices directly inferior to cerebral cortex to thalamus & basal ganglia Temporal amygdala ◦ Superior temporal gyrus -> Basal Ganglia primary auditory cortex ◦ Globes pallidus (GP) ◦ Wernicke's Area -> ◦ Caudate (C) comprehension of language ◦ Putamen (P) Limbic Diencephalon ◦ Thalamus (Th) ◦ Hypothalamus (H) sinus sagittal Paining I a Meninges of the Brain & Spinal Cord 3 layers Diencephalon ◦ Dura mater Thalamus ◦ Arachnoid mater ◦ Gatekeeper to the cortex ◦ Pia mater ◦ All sensory information Provide mechanical support of the CNS (except olfactory) passes Cerebrospinal uid (CSF) lled through thalamus subarachnoid space Hypothalamus ◦ Autonomic nervous and Dura Mater neuroendocrine control Tough mother Pineal Gland (Epithalamus) Thick, tough, collagenous membrane ◦ Endocrine gland ◦ Fused with the endosteum (inner periosteum) of the skull (dorsal) ◦ Produces melatonin ◦ Adheres to underlying arachnoid (ventral) Dural septa (folds) Brain stem ◦ Falx cerebra: 1st fold separates the left and right hemisphere Midbrain: optic chiasm to pons ◦ Tentorium cerebelli: separates the cerebellum from the brain Hindbrain With few exceptions, spaces do not exist on either side of the dural membrane ◦ Pons ◦ 2 potential spaces ◦ Medulla ‣ Epidural: between cranium and outer dural surface Attachment point for most cranial ‣ Subdural: within innermost dural layer, near arachnoid boarder* nerves Dura mater contains venous sinuses that drain the brain ◦ Cranial nerve re exes ◦ Superior sagittal sinus Long tract functions I ◦ Left and right transverse sinuses Ascending reticular activating ◦ Straight sinus system, anaesthesia attacks this ◦ Consciousness/awareness Arachnoid Mater Thin, avascular membrane in direct contact with dura mater Cerebellum Arachnoid trabecula: small strands of collagenous connective tissue within Longitudinal divisions the subarachnoid space ◦ Vermis ◦ Give arachnoid mater its spider web-like appearance ◦ Cerebellar hemispheres Arachnoid villi: small protrusion though dura mater into venous sinuses 3 lobes ◦ Reabsorption of CSF into venous system ◦ Anterior ◦ Posterior ◦ Flocculonodular (oldest) Subarachnoid Cisterns Functions Large pockets of subarachnoid space lled with CSF ◦ Coordination of trunk & Major cisterns (4): interpeduncular, pontine, limb movements quadrigeminal and cisterns magna ◦ Eye movements Stabilize inter cranial pressure  I Pia Mater 'Tender' mater Meninges & The Spinal Cord Same meninges as those surrounding the brain Thin, connective tissue layer in direct contact with with a few important differences surface of CNS ◦ 1. Vertebral canal contains an epidural Contact with arachnoid trabecula on other side space between periosteum and dura Cerebral arteries & veins surrounded by pia before ◦ 2. Pia mater gives rise to longitudinal entering/exiting the brain denticulate ligaments -> spinal cord ◦ Perivascular space anchor ◦ 3. Lumbar cistern at caudal end of spinal cord Ventricular System BE Igniting.gggIrggijanr Csfventricularflow Ding Ecifaffnback Md Aqueduct ofSylvius Hydrocephalus 'Water on the brain' Choroid Plexus: produces CSF CSF is constantly produced Ependymal cells line the lateral ventricles, pass Can be a result of excess CSF production, blockage of through the IV-foramen and roof of 3rd ventricles circulation or de cient CSF reabsorption Separate strand in 4th ventricle Enlargement of ventricles Component of the BBB Compression of brain tissue Specialized area where ependymal cells and pia Symptoms: headache, vomiting, nausea, papilledema, sleepy, mater are in direct contact coma Specialized ependymal cells -> choroid epithelium ◦ Infants: bulging of cranium ◦ Apical surface tight junctions Treatments: placement of a shunt to drain into lumbar system A young child presents with aqueductal stenosis (a narrowing of the aqueduct) due to a midbrain tumor. Which ventricular areas are/aren't affected? ◦ lateral ventricles and the 3rd ventricle are affected Increased surface area through folding Brain Circulation Total surface area >200cm2 Neurons lack the ability to store energy Rate of formation: 350 uL/min, 500mL/day, and oxygen anterior cerebral artery relatively constant Brain uses about 15% of normal middle artery c erebral cardiac output internalcarotid artery f Consumes 25% of the body's oxygen BloodsupplytoHindbrain Loss of consciousness after just 10 artery cerebral posterior big.EEEnesra seconds without perfusion Bam p.gg ngew isconnectionbetweeninternalcarotidandvertebral basilar in go.IEiointsn caabrancne YEingg medulla m EEE.io Functions of Circle of Willis EI.EE Normally, little blood is moved along anterior and EYYsqgerie uBgaEEIIiarI.im posterior communicating IEeenra arteries If one major vessel either within or proximal to the iII I Circle of Willis becomes is iii occluded, the communication arteries brain allow for perfusion of distal tissue II p E.IE IIaEgiiction Most effective when occlusion occurs slowly over time  Medialsurface Lateralsurface Deep Brain Structures Anterior choroidal artery (AChA) ◦ Branch of the ICA ◦ Blood supply of optic tract, choroid plexus of inferior lateral ventricle, thalamus and hippocampus Perforating (ganglionic) branches ◦ Small branches off ACA, MCA or PCA ◦ Blood supply of basal ganglia, internal capsule & rI diencephalon an ◦ Often compromised during stroke (stuff that breaks off from main clot can easily block these) Posterior choroidal arteries (PChA) i EEIaEFeYan ◦ Branches of the posterior cerebral artery ◦ Supply choroid plexus of lateral and 4th ventricle 7 Venous Return 2 sets of veins drain the brain Super cial Veins ◦ Lie on the surface of cerebral hemispheres ◦ Drain to superior sagittal sinus Venous Drainage Deep Veins Sagittal + straight sinus -> transverse sinus -> ◦ Drain structures in the sigmoid sinus -> internal jugular vein walls of the ventricles Vascular problems involving veins less common ◦ Converge on internal then arterial problems Regulation of blood ow cerebral veins Normal: ~ 55mL/100g brain per min ◦ Drain to straight sinus 3 major mechanisms 1. Autoregulation Angiography *** ask soph about image ◦ Blood vessels constrict/relax to maintain constant ow Injection of a radio plaque dye into the 2. Local Responses artery of interest, followed by ◦ Ex: Glutamate release from neurons (excitatory NT) radiographic imaging every 1-2 ◦ Binds to receptors on astrocytes -> release of vasodilators seconds, invasive ◦ Results in local increase in blood ow Identi cation of vascular pathologies 3. Autonomic Control such as aneurysms ◦ Least important regulatory factor ◦ May play role in longer term adaptations (Ex: stress) Aneurysms Balloon-like swellings of arterial walls Most often formed at or near arterial Cerebrovascular Accident/Stroke branch points Most common cause of neurological de cits Consequences Reduction in blood ow -> neuronal malfunction or death ◦ Compression of brain tissue Ischemic Stroke ◦ Rupture -> subarachnoid ◦ Sudden blockage of blood ow hemorrhage ◦ Early treatment can limit permanent damage to affected areas Transient ischemic attack (TIA)/mini stroke Hemorrhagic Stroke ◦ Arterial rupture, often of small perforating arteries Signs and symptoms depend by region(s) affected Circumventricular Organs (CVOs) Location where the cerebral capillaries are fenstrated & allow for relatively free communication Located around 3rd and 4th ventricles ftp.atepnotsiifeema Sensory Organs ◦ Area postrema: monitors blood for toxins, chloriaplexus induces vomiting (morning sickness, gravel aims to stop this), lies right under the 4th ventricle ◦ Vascular organ of the lamina terminalis (OVLT): regulation of uid balance ◦ Subfornical organ Secretory Organs ◦ Median eminence of hypothalamus and posterior pituitary: neuroendocrine role (secretes hormones into circulation) ◦ Pineal Gland: secretion of melatonin (biological clock)