Neurophysiology Part 1 - BMS 100 - Fall 2022 PDF

Neurophysiology Part 1 Basic Organization and Histology of the Nervous System Dr. Vargo BMS 100 Week 10 The Neurologic System Organization of the Nervous System Central, peripheral, enteric – a deeper dive Autonomic vs. somatic Organization of the autonomic nervous system Afferent fibres, effe...

Neurophysiology Part 1 Basic Organization and Histology of the Nervous System Dr. Vargo BMS 100 Week 10 The Neurologic System Organization of the Nervous System Central, peripheral, enteric – a deeper dive Autonomic vs. somatic Organization of the autonomic nervous system Afferent fibres, efferent fibres, and integration Histology and General Cellular Physiology of the Nervous System Structure and function of glial cells – astrocytes, oligodendrocytes, Schwann cells, microglia Neurons The ventricular system, CSF, the blood brain barrier, and their associated cells General Organization – Nervous System Brain Somatic Motor, cranial: Cranial skeletal muscles Cranial Nerves Spinal Cord Special Sensory: Hearing, equilibrium, sight, smell, taste Cranial Somatic Sensory Cranial Nerves Visceral Sensory: stretch, pain, temperature, chemical stimuli Cranial & Spinal Nerves Somatic Sensory, non-cranial: Touch, pain, pressure, vibration, temperature Spinal Nerves Visceral motor: Parasympathetic nervous system Cranial Nerves Somatic Motor, non-cranial: non-cranial skeletal muscles Spinal Nerves Visceral motor: autonomic nervous system – all SNS and sacral PaNS Spinal Nerves Key Nervous System Terms • White matter – collections of myelinated axons in the central nervous system § Myelin = an multi-layer lipid coat that “insulates” axons formed by specialized glial cells in the peripheral (PNS) and central nervous system (CNS) § Although both the PNS and CNS have myelinated axons, only the CNS has white matter § Myelin increases the velocity signal transmission along an axon • Grey matter – areas of the central nervous system that have relatively few myelinated axons § mostly comprised of neuronal and glial cell bodies • Tract = a collection of axons in the CNS § Large tracts are usually white matter • Nerve = a collection of axons in the PNS Neurons - review The longer an axon is, and the more “crucial” the information it carries à the more likely that it will be myelinated • Dendrites connect with other neurons via synapses § Dendrites • Inputs from other neurons are integrated à “decision” made, based on inputs, regarding whether the neuron will send a signal § Cell body, axon hillock are the sites of integration • If the stimuli that the neuron receives excite it enough à send a signal down the axon • axon Gray vs. White Matter • The dorsal columns are examples of tracts • Much of the volume of the cerebral cortex is white matter § Gray matter forms a relatively thin layer superficially General Organization – Nervous System Brain Spinal Cord Red circles – PNS connections with the CNS CNS – brain, spinal cord How does the peripheral nervous system (PNS) differ from the central nervous system (CNS)? • Different cells populate the PNS • See later this lecture • Axons/nerves in the PNS can sometimes regenerate after damage • Does not happen in the CNS • The PNS is much less “isolated” than the CNS – cells of the immune system are allowed to enter and exit the PNS more freely • Fewer neuronal cell bodies in the PNS versus the CNS Key Nervous System Terms • Ganglia – collections of neuronal cell bodies in the peripheral nervous system § Examples – dorsal root ganglia and sympathetic trunk ganglia adjacent to the vertebrae • Nuclei – collections of neuronal cell bodies in the central nervous system § Examples – the basal nuclei, the supra-optic nucleus (remember ADH?) and the paraventricular nucleus (remember oxytocin?) § The basal nuclei are often known as the basal ganglia – widely accepted misnomer • Both nuclei and ganglia will contain axons, but more of the volume of these structures is devoted to neuronal and glial cell bodies Central Nervous System Histology • Glial cell types: § Astrocytes § Oligodendrocytes § Microglia • Fluid spaces within the CNS § Ventricles, ependymal cells, choroid plexus § Interstitial fluid • Nature of the blood-brain barrier (BBB) General Histology of The CNS Astrocytes • Most numerous cells in the CNS, highest numbers in the gray matter § Roughly 8 - 10X more astrocytes in the CNS than neurons § Name means “star-cells” – many cellular processes that makes them look like stars (stellate) • Critical role in CNS physiology: § Facilitate the formation and strengthening of synapses (neuroplasticity) § Regulate the concentration of ions in the interstitial fluid • K+, Na+, Cl-, HCO3-, Ca+2 § Structural support for the brain • Intermediate filament – GFAP (glial fibrillary acidic protein) § Barrier functions – induce the formation of the BBB at the brain microvasculature, form a “limiting membrane” at the external CNS surface § “Feed” neurons – help extract nutrients from the blood, provide nutrients to neurons to support energy metabolism Astrocytes • Astrocytes are connected to each other via gap junctions § Small “tunnels” that connect the intracellular fluid of astrocytes to each other (span the cell membranes and connect cell to cell) in a network known as a syncytium • “waves” of calcium increases and general depolarization that move through the brain, astrocyte-to-astrocyte have been observed § may help the effectiveness of neuronal signaling and neuroplasticity – being actively studied P = astrocyte process S = astrocyte soma (cell body) Oligodendrocytes • Have many processes § Each process wraps around the axon of a CNS neuron many times, “sheathing” the axon in myelin § Myelin sheath = compacted layers of cell membrane rich in sphingolipids that have very little cytosol • Function of myelin: § Increases the speed with which an action potential moves down an axon § Reduces the energy consumed by movement of an action potential down an axon – more efficient signaling • Roughly twice as many oligodendrocytes as neurons in the CNS Microglial cells • Small-bodied glial cells that: § Remove (phagocytosis) cellular debris § Monitor the environment and fight pathogens § If the pathogen cannot be eliminated by resident microglia, they “call in” other white blood cells through secretion of soluble factors (cytokines) and can present antigen to other immune cells • Derived from blood-borne immune cells (monocytes) that migrate into the CNS § Roughly as numerous as neurons in the CNS The Ventricular System and Cerebrospinal Fluid • The brain and spinal cord are surrounded by cerebrospinal fluid – roughly 150 mL total § Around the periphery of the brain à subarachnoid space § Within particular compartments of the brain à 4 ventricles (shown at right) § Within the subarachnoid space and central canal of the spinal cord • CSF is a specialized fluid formed from the choroid plexus – a complex of capillaries and epithelial cells § Mostly located in the lateral ventricles The Ventricular System and Cerebrospinal Fluid CSF production & circulation: • Produced in the floor of the lateral ventricle by the choroid plexus • Moves from the lateral ventricles à 3rd ventricle à 4th ventricle (see right) • Circulates into the subarachnoid space and down the spinal cord • Eventually absorbed by specialized structures known as arachnoid granulations § Transport CSF fluid into venous structures Basic CSF Physiology • Ependymal cells that line the ventricles are ciliated – movement of cilia drives the movement of CSF • CSF production is carefully regulated in the choroid plexus § Selectively transports water, electrolytes, nutrients from blood to CSF § Tight junctions prevent unwanted substances from entering the CSF • The interstitial fluid (extracellular fluid) of the brain and spinal cord is formed by: § Filtration of CSF from the ventricles through the ependymal cells § Regulated filtration of fluid through capillaries deeper in the CNS tissue The Blood Brain Barrier • The central nervous system is isolated/protected from a number of factors that can circulate through the bloodstream § Immune cells • White blood cells attack pathogens and remove cellular debris • The CNS structure is delicate, and its function depends on its precise architecture – usually white blood cells aren’t allowed into the CNS § Exception – microglial cells § Noxious wastes and toxins § Pathogens The Blood Brain Barrier • Most capillaries in the body are quite leaky § Nutrients, electrolytes, water, metabolites filter through easily – few tight junctions § Immune cells cross capillaries with little difficulty when endothelial cells express signals to call them in • Astrocytes contact capillaries in the CSF via structures known as endfeet § Endfeet cause increased tight junction expression in capillary endothelial cells § Endfeet also “tell” capillaries what to transport into the CNS tissue • Cause endothelial cells to express transport proteins for desirable molecules and inhibit expression of pro-inflammatory signals Astrocytic end-feet Capillary endothelial cell Peripheral Nervous System Histology • Nerve and ganglion structure • Nature of the Blood-Nerve Barrier (BNB) • Glial cell types: § Schwann Cells § Satellite cells Structure of a Nerve • Epineurium – strong, fibrous connective tissue covering that surrounds each nerve § Blood vessels run within this layer – known as the vasa nervorum • Perineurium – surrounds bundles of axons (some myelinated, some not) known as fascicles § The perineurium is formed by fibroblast-like cells arranged in sheets 2-6 cells thick § Tight junctions are found between these cells – therefore the perineural layer can regulate what moves into the fascicle • Endoneurium – delicate connective tissue layer that surrounds individual axons • See next slide for images Structure of a Nerve The Blood-Nerve Barrier (BNB) • Barrier 1 – the cells of the perineurium and the tight junctions between them • Barrier 2 – the endothelial cells that line the capillaries within the fascicles also express many tight junctions • Both barriers actively regulate the movement of ions and immune cells into the fascicles • The BNB is much more permissive to the entrance of white blood cells (leukocytes) than the BBB § May relate to the ability of peripheral nerves to regenerate after being severed § White blood cells are crucial for repair in most tissues – as we will see when we study chronic inflammation Glial Cells of the PNS • Schwann cells – provide the myelin sheath for axons within fascicles • Differ from oligodendrocytes in that one cell only myelinates one axon § Each oligodendrocyte myelinates multiple nearby axons § Schwann cells can extend as far as 1 mm along an axon Glial Cells of the PNS • Satellite cells surround, protect, and nourish neuronal cell bodies located in ganglia § Interestingly, they do not establish a “blood-ganglion barrier” – the dorsal root ganglia and autonomic ganglia don’t seem to need one • Multiple satellite cells are closely apposed to neuronal cell bodies § Nutritional and ionic homeostasis roles Structure and Function of Neurons - I • Morphology and Cell Biology of Neurons § Key components of neurons • • • • Dendrites, dendritic spines, and synapses Structures of the soma The axon, axon hillock, and synaptic terminals Axonal transport § Neuronal morphology • Multipolar - types • Pseudo-unipolar and bipolar - locations Neuronal Morphology – Dendrites • Dendrites are the “input” area of the neuron § Usually multiple processes that connect to the soma (body) of the neuron § Dendritic spines stud dendrites – the spines are positioned very close to axon terminals to form synapses • Spines and axon terminals are almost touching – about 20 nm apart § The morphologic relationship of the dendritic spine to the axon terminal can influence the effectiveness of the synapse • More “effective” dendritic spines are ones that carry more information to the rest of the neuron – they tend to be larger, broader, and “mushroom-shaped” • More about synaptic physiology next lecture Dendrites, Axon Terminals, and Synapses – a simple view Axon terminal Dendritic spine Note the many axon terminals, the close apposition of axon terminal and dendritic spine to form the synapse on the dendrite Dendrites and Dendritic Spines - Details • Spine maturation makes the synapse more effective § The “filopodia” dendritic spine below is immature and “looking for a connection” with an axon terminal § The “mushroom” and “branched” spines were shown to elicit more effective neuronal responses when they are stimulated § Axon terminals not shown in this diagram The Neuronal Cell Body (Soma) • Site of protein synthesis for the rest of the neuron § Nissl substance = basophilic area nearby the nucleus composed of lots of free ribosomes and rER • The larger the neuron and the more extensive the processes, the more protein synthesis is necessary • Microtubules, actin microfilaments, and neurofilaments found in the body and in the processes of neurons § Neurofilaments = intermediate filaments that are more concentrated in axons – provide structural stability for neuronal processes § Microtubules have opposite orientation in dendrites vs. axons – this is arranged in the cell body • Ensures that dendritic and axonal components are directed to the right places NS – Nissl substance The Axon Hillock, Axon, and Synaptic Terminals • The axon, axon hillock, and synaptic terminals are the sites of a unique electrical phenomenon of the cell membrane known as an action potential § Rapid depolarization of the cell membrane generated by particular ion channels in a positive feedback fashion – more next day • Axons can be myelinated by Schwann cells (PNS) or oligodendrocytes (CNS) § Myelin sheaths are separated by myelin-free segments known as nodes of Ranvier à crucial to action potential generation (more next lecture) General Morphology of Neurons • Pseudo-unipolar neurons A § These neurons have a distal process that either interacts with a sensory receptor or serves as a sensory receptor (A) § The proximal process synapses in the CNS (B) § The process that connects A to B behaves as an axon • It conducts action potentials (next lecture) § Typical of dorsal root ganglion cells – somatic sensation B General Morphology of Neurons • Bipolar neurons A § These neurons have a distal process (A) that acts as a dendrite – it either serves as a sensory receptor or interacts with a sensory receptor § The proximal process synapses in the CNS – it is an axon and conducts action potentials (B) § Typical of neurons that detect the special senses – vision, hearing, smell B General Morphology of Neurons • Multipolar neurons § The most common neurons § Dendrites receive information from other neurons via synaptic terminals § The cell body summates and integrates this information § The axon carries action potentials to: • Other neurons • Glands • Muscle tissue § Typical of all interneurons and somatic motor neurons General Organization – Sensory System Brain Spinal Cord Afferent = nerves that carry (sensory) information to the central nervous system Cranial nerve afferents: • Special Senses • CN I, II, VII, VIII, IX, X • Somatic Senses • Mostly CN V • Visceral Sensory Special Sensory: Hearing, equilibrium, sight, smell, taste Cranial Somatic Sensory Cranial Nerves Visceral Sensory: stretch, pain, temperature, chemical stimuli Cranial & Spinal Nerves Somatic Sensory, non-cranial: Touch, pain, pressure, vibration, temperature Spinal Nerves • CN IX and X • Baroreceptors • Visceral sensation from most of the alimentary tract, lungs, heart Key Nervous System Concept - Sensation • Sensation is composed of a number of distinct steps (not all need to be present): § Detection of a physical/chemical stimulus by some type of receptor • i.e. light, pressure, chemical changes in the GI tract, scents, length of a muscle, stretch of a hollow organ… § Transduction – transforming the physical stimulus into an electrical impulse that can be carried along an axon § Other neurons at various levels of the central nervous system can detect the electrical impulse and modify its intensity and route the signal to various CNS locations § Perception – conscious awareness of the sensation – this occurs at the level of the cortex • Some sensory afferent information is not perceived à osmolarity, blood pressure, etc. Review – cranial nerves General Organization – Sensory System Brain Spinal Cord Afferent = nerves that carry (sensory) information to the central nervous system Cranial nerve afferents: Review: • Special Senses • Pathways? • Cortical regions for • CN I, II, VII, VIII, IX, X perception? • Somatic Senses • General area of • Mostly CN V the brainstem? • Visceral Sensory Special Sensory: Hearing, equilibrium, sight, smell, taste Cranial Somatic Sensory Cranial Nerves Visceral Sensory: stretch, pain, temperature, chemical stimuli Cranial & Spinal Nerves Somatic Sensory, non-cranial: Touch, pain, pressure, vibration, temperature Spinal Nerves • CN IX and X • Baroreceptors • Visceral sensation from most of the alimentary tract, lungs, heart General Organization – Sensory System Brain Spinal Cord Special Sensory: Hearing, equilibrium, sight, smell, taste Cranial Somatic Sensory Cranial Nerves Afferents that ascend through the spinal cord: • Somatic sensation below the neck • Skin receptors – pain, temperature, fine and coarse touch, vibration • Joint and intra-muscular receptors – golgi tendon organs, muscle spindles, joint receptors à proprioception Visceral Sensory: stretch, pain, temperature, chemical stimuli Cranial & Spinal Nerves Somatic Sensory, non-cranial: Touch, pain, pressure, vibration, temperature Spinal Nerves • Visceral Sensation • Distal portions of the colon • Bladder • Reproductive organs Dorsal Column System and Spinothalamic Tract Review Motor Output – Key Nervous System Concept • After sensory input is integrated – usually by circuits involving multiple neurons – then a motor response frequently occurs • Motor system = a motor neuron synapses with some sort of effector so that it can activate it when the neuron is excited § Excitation = multiple electrical signals travelling down the axon – known as action potentials § Examples of effectors: • Skeletal muscle (voluntary movements) • Smooth muscle (blood vessels, GI tract, genitourinary tract, respiratory tract) • Glands (endocrine or exocrine) General Organization – Motor System Brain Spinal Cord Somatic Motor, non-cranial: non-cranial skeletal muscles Spinal Nerves Somatic Motor, cranial: Cranial skeletal muscles Cranial Nerves Visceral motor: autonomic nervous system – all SNS and sacral PNS Spinal Nerves Visceral motor: Parasympathetic nervous system Cranial Nerves • Efferents = neurons that carry information from the CNS to the peripheral nervous system • Somatic Motor efferents – control of skeletal muscles • Usually voluntary • Some we don’t have conscious control over (i.e. middle ear muscles) General Organization – Motor System Brain Spinal Cord Somatic Motor, non-cranial: non-cranial skeletal muscles Spinal Nerves Somatic Motor, cranial: Cranial skeletal muscles Cranial Nerves Visceral motor: autonomic nervous system – all SNS and sacral PNS Spinal Nerves Visceral motor: Parasympathetic nervous system Cranial Nerves • Major cranial nerves – somatic motor: • CN VII, V, XI • CN IX, X, XII • CN III, IV, VI • What general muscles do each of these cranial nerves control? • Why are they grouped in those 3 bullet points? (pattern?) Corticospinal tract Review • Efferents for skeletal muscles below the neck are part of the corticospinal tract § Axons from neurons in the pre-central gyrus decussate and descend down the spinal cord à § Synapse on anterior horn motor neuron à § Axon of anterior horn motor neuron exits the central nervous system as a spinal nerve General Organization – Motor System Brain Spinal Cord Somatic Motor, non-cranial: non-cranial skeletal muscles Spinal Nerves Somatic Motor, cranial: Cranial skeletal muscles Cranial Nerves Visceral motor: autonomic nervous system – all SNS and sacral PNS Spinal Nerves Visceral motor: Parasympathetic nervous system Cranial Nerves • Visceral motor efferents – cranial nerve PaNS: • CN X – PaNS control for the heart, lungs, majority of the GI system • CN III – PaNS control over pupillary muscles • CN VII, IX – PaNS control over salivary, tear glands General Organization – Motor System Brain Spinal Cord Somatic Motor, non-cranial: non-cranial skeletal muscles Spinal Nerves Somatic Motor, cranial: Cranial skeletal muscles Cranial Nerves Visceral motor: autonomic nervous system – all SNS and sacral PNS Spinal Nerves Visceral motor: Parasympathetic nervous system Cranial Nerves • Visceral motor efferents – spinal nerve ANS & PaNS: • SNS control for the heart, lungs, proximal GI tract • SNS control for pupillary muscles, salivary glands, tear glands • SNS and PaNS control for distal GI tract, reproductive structures, bladder The Autonomic Nervous System • Sympathetic Nervous System • Parasympathetic Nervous System • Enteric Nervous System § More when we cover the GI system next semester The Sympathetic Nervous System • “Fight or Flight” § Increases heart rate and cardiac output § Improves ventilation § Decreases digestive function § Increases glucose availability (gluconeogenesis, glycogenolysis) § Increases blood flow to skeletal muscles, heart § Decreases blood flow to GI tract, skin, kidneys § Major hormones/neurotransmitters: epinephrine and norepinephrine The Sympathetic Nervous System - Organization • Note the presence of ganglia § adjacent to the vertebral column à paravertebral ganglia § Anterior to vertebral column à prevertebral ganglia • i.e. celiac, superior mesenteric ganglia The Parasympathetic Nervous System • “Rest and digest” § Decreases heart rate and cardiac output § Bronchoconstriction and increased mucous secretion § Increases digestive function and GI motility § Increases blood flow to digestive tract § Major neurotransmitter: acetylcholine Parasympathetic Nervous System Organization • Note the two paths: § Vagus nerve – all of the visceral efferents up to the proximal large bowel § Sacral nerves – all of the visceral efferents to the rest of the large bowel, kidney, reproductive organs § Ganglia are located closer to target organs