Fundamentals of the Nervous System PDF

Fundamentals of the Nervous System Nikolai P Pace Three major functions: ▪ Sensory – monitors internal & external environment through presence of receptors ▪ Integration – interpretation of sensory information (information processing); complex (...

Fundamentals of the Nervous System Nikolai P Pace Three major functions: ▪ Sensory – monitors internal & external environment through presence of receptors ▪ Integration – interpretation of sensory information (information processing); complex (higher order) functions ▪ Motor – response to information processed through stimulation of effectors ▪ muscle contraction ▪ glandular secretion General Organization of the nervous system Two Anatomical Divisions – Central nervous system (CNS) Brain in cranial cavity Spinal cord in spinal canal – Peripheral nervous system (PNS) All the neural tissue outside CNS Afferent division (sensory input to CNS) Efferent division (motor output from CNS) Two Functional divisions Somatic nervous system – provides sensory and motor innervation to all body except viscera, smooth muscle and glands Autonomic nervous system - – Sympathetic, parasympathetic and enteric – Efferent involuntary motor innervation to smooth muscle, myocardium and glands and afferent sensory innervation from viscera (pain and autonomic reflexes) General Organization of the nervous system Brain & spinal cord Somatic vs Visceral sensation Somatic vs Visceral sensation  Histology of neural tissue Two types of neural cells in the nervous system: ▪ Neurons – ▪ For processing, transfer, and storage of information. ▪ Consist of a cell body and processes of varying length ▪ Arranged as an integrated communications network ▪ Contacts between neurons called synapses ▪ Neuroglia – For physical support, regulation & protection of neurons. ▪These are non-conducting cells in apposition to neurons.  Neuroglia (glial cells) CNS neuroglia: astrocytes oligodendrocytes microglia ependymal cells PNS neuroglia: Schwann cells (neurolemmocytes). satellite cells in ganglia  Astrocytes create supportive framework for neurons create “blood-brain barrier” monitor & regulate interstitial fluid surrounding neurons secrete chemicals for embryological neuron formation stimulate the formation of scar tissue secondary to CNS injury  Oligodendrocytes create myelin sheath around axons of neurons in the CNS. Myelinated axons transmit impulses faster than unmyelinated axons Microglia “brain macrophages” phagocytize cellular wastes & pathogens  Ependymal cells line ventricles of brain & central canal of spinal cord produce, monitor & help circulate CSF (cerebrospinal fluid)  Schwann cells surround all axons of neurons in the PNS creating a neurilemma around them. Neurilemma allows for potential regeneration of damaged axons creates myelin sheath around most axons of PNS Satellite cells support groups of cell bodies of neurons within ganglia of the PNS Myelin in the Peripheral and Central Nervous Systems In multiple sclerosis (MS), patches of myelin are destroyed in the brain and spinal cord  Schwann cells – Myelin sheath – Neurolemma (nucleus and most of cytoplasm squeezed to outside)  Neuron Structure Neurons are the structural and functional units Sensory neurons : – convey impulses from receptors to CNS – Somatic afferent : pain , temperature, touch and pressure from body surface and pain and proprioreception from muscles/tendons/joints – Visceral afferent :pain from mucosae, glands and blood vessels Motor neurons : – Convey impulses from CNS or ganglia to effector cells – Somatic efferent : voluntary impulses to skeletal muscle – Visceral efferent : voluntary impulses to smooth muscle, glands and cardiac conducting tissue Interneurons: – Form a communicating and integrating network between sensory and motor neurons Neuron structure All have a cell body: with nucleus and cytoplasm Cell bodies are in clusters – CNS: clusters called nuclei – PNS: clusters are called ganglia (are outside the CNS)  Dendrites impulse Conducts impulses towards the cell body Typically short, highly branched & unmyelinated Surfaces specialized for contact with other neurons Contains neurofibrils & Nissl bodies  Axons Conduct impulses away from cell body Long, thin cylindrical process of cell Arises at axon hillock Impulses arise from initial segment (trigger zone) Side branches (collaterals) end in fine processes called axon terminals Swollen tips called synaptic end bulbs contain vesicles filled with neurotransmitters 25  Most axons of the nervous system are surrounded by a myelin sheath (myelinated axons) of Ranvier The presence of myelin speeds up the transmission of action potentials along the axon Myelin will get laid down in segments (internodes) along the axon, leaving unmyelinated gaps known as nodes of Ranvier Regions of the nervous system containing groupings of myelinated axons make up the white matter gray matter is mainly comprised of groups of neuron cell bodies, dendrites & synapses (connections between neurons)  Neuron processes Nerve fibers = axons – Nerve impulse generators & transmitters – One per neuron, although can branch into “collaterals” – At terminal end branch a lot (e.g. 10,000/terminus) Receptive regions called dendrites – Have receptors for neurotransmitters (chemicals released by other neurons) – Neurons may have many Run through CNS in tracts of white matter Run through the PNS forming peripheral nerves  Classification of neurons Structural classification based on number of processes coming off of the cell body: Anaxonic neurons no anatomical clues to determine axons from dendrites functions unknown Multipolar neuron multiple dendrites & single axon most common type Motor neurons and interneurons are multipolar Bipolar neuron two processes coming off cell body – one dendrite & one axon True bipolar neurons are limited to the retina and the ganglia of the vestibulocochlear nerve (CN VIII) of the ear Unipolar (pseudounipolar) neuron single process coming off cell body, giving rise to dendrites (at one end) & axon (making up rest of process) Cell bodies of sensory neurons lie in dorsal root ganglia close to CNS One axonal branch extends peripherally and one axonal branch extends to the CNS Known as pseudounipolar as during embryogenesis they are initially bipolar but become unipolar as their processes migrate and fuse into a single process  Classification of neurons Functional classification based on type of information & direction of information transmission: Sensory (afferent) neurons – transmit sensory information from receptors of PNS towards the CNS most sensory neurons are unipolar, a few are bipolar Motor (efferent) neurons – transmit motor information from the CNS to effectors (muscles/glands/adipose tissue) in the periphery of the body all are multipolar Association (interneurons) – transmit information between neurons within the CNS; analyze inputs, coordinate outputs are the most common type of neuron (20 billion) are all multipolar  Conduction across synapses In order for neural control to occur, action potentials must not only be conducted along nerve cells, but must also be transferred from one nerve cell to another across a synapse Most synapses within the nervous system are chemical synapses, & involve the release of a neurotransmitter  Synapses Neurons communicate with each other and with effector cells via synapses These are specialized junctions between neurons that – Transmit an AP from a presynaptic to a postsynaptic neuron, OR – Transmit an AP between axons and target cells, e.g muscle or glands Classified morphologically – Axodendritic (between axons and dendrites) – Axosomatic (between axons and cell bodies) – Axoaxonic (between axons) Not resolvable in routine H&E but visible using silver precipitation stains Neurons can synapse with: 1. Neurons 2. Muscle 3. Glands  The Structure of a Typical Synapse Typical synapses consist of a synaptic knob, a synaptic cleft and a postsynaptic membrane  Synapses The presynaptic knob is the end of the neuron process from which the neurotransmitters are released. – Characterised by multiple synaptic vesicles that contain neurotransmitters – Typically numerous mitochondria – N-ethylmaleimide sensitve factor (NSF) is required for the formation and fusion of synaptic vesicles with the pre-synaptic membrane Synaptic cleft – 20-30nm space separating pre- from post- synaptic neurons Post-synaptic membrane – Contains receptors for the neurotransmitter  Neuronal Circuits 1. Diverging -- single cell stimulates many others 2. Converging -- one cell stimulated by many others 3. Reverberating -- impulses from later cells repeatedly stimulate early cells in the circuit (short-term memory) 4. Parallel-after-discharge -- single cell stimulates a group of cells that all stimulate a common postsynaptic cell (math problems)  Neuronal Circuits 1. Diverging -- single cell stimulates many others 2. Converging -- one cell stimulated by many others 3. Reverberating -- impulses from later cells repeatedly stimulate early cells in the circuit (short-term memory) 4. Parallel-after-discharge -- single cell stimulates a group of cells that all stimulate a common postsynaptic cell (math problems)  Neuronal Circuits 1. Diverging -- single cell stimulates many others 2. Converging -- one cell stimulated by many others 3. Reverberating -- impulses from later cells repeatedly stimulate early cells in the circuit (short-term memory) 4. Parallel-after-discharge -- single cell stimulates a group of cells that all stimulate a common postsynaptic cell (math problems)  Neuronal Circuits 1. Diverging -- single cell stimulates many others 2. Converging -- one cell stimulated by many others 3. Reverberating -- impulses from later cells repeatedly stimulate early cells in the circuit (short-term memory) 4. Parallel-after-discharge -- single cell stimulates a group of cells that all stimulate a common postsynaptic cell (problem solving)  Anatomical organization of neurons Neurons of the nervous system tend to group together into organized bundles The axons of neurons are bundled together to form nerves in the PNS & tracts/pathways in the CNS. Most axons are myelinated so these structures will be part of “white matter” The cell bodies of neurons are clustered together into ganglia in the PNS & nuclei/centers in the CNS. These are unmyelinated structures and will be part of “gray matter” Neural Tissue Organization  Peripheral Nerves Composed of bundles of nerve fibres held together by connective tissue called the perineurium An epineurium surrounds the whole nerve An endoneurium surrounds individual neurons Each nerve fiber consists of an axon surrounded by a cellular investment called the neurilemma or the sheath of Schwann Peripheral Nerve CS x 200 Epineurium – dense connective tissue covering whole nerve Adipose tissue top right Section shows several bundles of nerve fibres x 200 Peripheral Nerve CS x640 Perineurium surrounding bundles of nerves Each nerve fibre is composed of a central axon, surrounded by myelin space External to myelin is a thin cytoplasmic rim representing the neurilemma Occasional Schwann cell nuclei Peripheral Nerve LS x 200 Epineurium at left Within nerve bundle, the nerve fibres show a characteristic wavy pattern Peripheral Nerve LS x640 Nerve fibres in longitudinal profile Central axon Surrounded by a myelin space Bounded by the cytoplasmic band of neurilemma cell Node of Ranvier in myelinated fibres where the ends of two Schwann cells meet – a constriction of the neurilemma  Sympathetic and Dorsal Root Ganglia Ganglia are clusters of neuronal bodies located outside the CNS Sensory ganglia – contain cell bodies of sensory nerves that carry impulses to CNS Autonomic ganglia – peripheral motor ganglia of the ANS that contain the cell bodies of post synaptic neurons that conduct to smooth muscle, cardiac muscle and glands – Synapses between presynaptic neurons [cell bodies in CNS] and post-synaptic neurons occur in autonomic ganglia – Sympathetic ganglia are located in the sympathetic chain in the paravertebral ganglia and on the anterior surface of the aorta [prevertebral ganglia]. – They send long postsynaptic neurons to viscera – Parasympathetic [terminal] ganglia are located close to or in the organs that they innervate via their post synaptic neurons. – Enteric ganglia are located in the submucosal plexus and in the myenteric plexus of GIT Sympathetic and Dorsal Root Ganglia x160 Nerve fibres Blood vessels Cell bodies of post synaptic neurones Sympathetic and Dorsal Root Ganglia x 500 Large cell bodies with multiple processes Large pale-staining spherical nuclei which contains a speherical dark nucleolus indicate active protein synthesis Spinal Cord An outer white matter containing ascending and descending nerve fibres An inner gray matter that contains cell bodies of neurons as well as nerve fibres H- shaped surrounding a central canal with dorsal and ventral horns Ventral horns contain the large cell bodies of motor neurons  Runs through the vertebral canal Spinal Cord Extends from foramen magnum to second lumbar vertebra Regions – Cervical – Thoracic – Lumbar – Sacral – Coccygeal Gives rise to 31 pairs of spinal nerves – All are mixed nerves Not uniform in diameter – Cervical enlargement: supplies upper limbs – Lumbar enlargement: supplies lower limbs Conus medullaris- tapered inferior end – Ends between L1 and L2 Cauda equina - origin of spinal nerves extending inferiorly from conus medullaris.  Connective tissue membranes Meninges – Dura mater: outermost layer; continuous with epineurium of the spinal nerves – Arachnoid mater: thin and wispy – Pia mater: bound tightly to surface Forms the filum terminale – anchors spinal cord to coccyx Forms the denticulate ligaments that attach the spinal cord to the dura Spaces – Epidural: external to the dura Anesthestics injected here Fat-fill – Subdural space: serous fluid – Subarachnoid: between pia and arachnoid Filled with CSF  Anterior median fissure and posterior Cross Section median sulcus – deep clefts partially separating left and right halves of Spinal Cord Gray matter: neuron cell bodies, dendrites, axons – Divided into horns Posterior (dorsal) horn Anterior (ventral) horn Lateral horn White matter – Myelinated axons – Divided into three columns (funiculi) Ventral Dorsal lateral – Each of these divided into sensory or motor tracts  Cross section of Spinal Cord Commissures: connections between left and right halves – Gray with central canal in the center – White Roots – Spinal nerves arise as rootlets then combine to form dorsal and ventral roots – Dorsal and ventral roots merge laterally and form the spinal nerve  Organization of Spinal Cord Gray Matter Recall, it is divided into horns – Dorsal, lateral (only in thoracic region), and ventral Dorsal half – sensory roots and ganglia Ventral half – motor roots Based on the type of neurons/cell bodies located in each horn, it is specialized further into 4 regions – Somatic sensory (SS) - axons of somatic sensory neurons – Visceral sensory (VS) - neurons of visceral sensory neur. – Visceral motor (VM) - cell bodies of visceral motor neurons – Somatic motor (SM) - cell bodies of somatic motor neurons  White Matter in the Spinal Cord Divided into three funiculi (columns) – posterior, lateral, and anterior – Columns contain 3 different types of fibers (Ascend., Descend., Trans.) Fibers run in three directions – Ascending fibers - compose the sensory tracts – Descending fibers - compose the motor tracts – Commissural (transverse) fibers - connect opposite sides of cord  White Matter Fiber Tract Generalizations Pathways decussate (most) Most consist of a chain of two or three neurons Most exhibit somatotopy (precise spatial relationships) All pathways are paired – one on each side of the spinal cord White Matter: Pathway Generalizations  Descending (Motor) Pathways Descending tracts deliver motor instructions from the brain to the spinal cord Divided into two groups – Pyramidal, or corticospinal, tracts – Indirect pathways, essentially all others Motor pathways involve two neurons – Upper motor neuron (UMN) – Lower motor neuron (LMN) aka ‘anterior horn motor neuron” (also, final common pathway)  Pyramidal (Corticospinal) Tracts Originate in the precentral gyrus of brain (aka, primary motor area) – I.e., cell body of the UMN located in precentral gyrus Pyramidal neuron is the UMN – Its axon forms the corticospinal tract UMN synapses in the anterior horn with LMN – Some UMN decussate in pyramids = Lateral corticospinal tracts – Others decussate at other levels of s.c. = Anterior corticospinal tracts LMN (anterior horn motor neurons) – Exits spinal cord via anterior root – Activates skeletal muscles Regulates fast and fine (skilled) movements  Corticospinal tracts 1. Location of UMN cell body in cerebral cortex 2. Decussation of UMN axon in pyramids or at level of exit of LMN 3. Synapse of UMN and LMN occurs in anterior horn of s.c. 4. LMN axon exits via anterior root  Extrapyramidal Motor Tracts Includes all motor pathways not part of the pyramidal system Upper motor neuron (UMN) originates in nuclei deep in cerebrum (not in cerebral cortex) UMN does not pass through the pyramids! LMN is an anterior horn motor neuron This system includes – Rubrospinal – Vestibulospinal – Reticulospinal – Tectospinal tracts Regulate: – Axial muscles that maintain balance and posture – Muscles controlling coarse movements of the proximal portions of limbs – Head, neck, and eye movement  The Autonomic Nervous System Regulate activity of smooth muscle, cardiac muscle & certain glands Structures involved – general visceral afferent neurons – general visceral efferent neurons – integration center within the brain Receives input from limbic system and other regions of the cerebrum  Autonomic versus Somatic NS Somatic nervous system – consciously perceived sensations – excitation of skeletal muscle – one neuron connects CNS to organ Autonomic nervous system – unconsciously perceived visceral sensations – involuntary inhibition or excitation of smooth muscle, cardiac muscle or glandular secretion – two neurons needed to connect CNS to organ preganglionic and postganglionic neurons  Autonomic versus Somatic NS Notice that the ANS pathway is a 2 neuron pathway while the Somatic NS only contains one neuron.  Basic Anatomy of ANS Preganglionic neuron – cell body in brain or spinal cord – axon is myelinated type B fiber that extends to autonomic ganglion Postganglionic neuron – cell body lies outside the CNS in an autonomic ganglion – axon is unmyelinated type C fiber that terminates in a visceral effector Divisions of the ANS 2 major divisions – parasympathetic – sympathetic Dual innervation – one speeds up organ – one slows down organ – Sympathetic NS increases heart rate – Parasympathetic NS decreases heart rate Sources of Dual Innervation Sympathetic (thoracolumbar) division – preganglionic cell bodies in thoracic and first 2 lumbar segments of spinal cord Parasympathetic (craniosacral) division – preganglionic cell bodies in nuclei of 4 cranial nerves and the sacral spinal cord Locations of Autonomic Ganglia Sympathetic Ganglia – trunk (chain) ganglia near vertebral bodies – prevertebral ganglia near large blood vessel in gut celiac superior mesenteric inferior mesenteric Parasympathetic Ganglia – terminal ganglia in wall of organ  Structures of Sympathetic NS Preganglionic cell bodies at lateral horns of T1 to L2 segments of the spinal cord Pre-ganglionic fibers – leave through the ant root of spinal nerve along with somatic motor fibers at the same segmental level They exit through the inter-vertebral foramina Pre-ganglionic fibers are myelinated – white rami gray ramus = unmyelinated = postganglionic fibers Postganglionic cell bodies –sympathetic chain ganglia along the spinal column –prevertebral ganglia at a distance from spinal cord –sweat glands, arrector pili mm., blood vessels to skin & skeletal mm. Ganglia & Plexuses of Sympathetic NS  Organs Innervated by Sympathetic NS Structures innervated by each spinal nerve Thoracic & cranial plexuses supply: – heart, lungs,esophagus & thoracic blood vessels – plexus around carotid artery to head structures Splanchnic nerves to prevertebral ganglia supply: – GI tract from stomach to rectum, urinary & reproductive organs  Circuitry of Sympathetic NS Divergence = each preganglionic cell synapses on many postganglionic cells Mass activation due to divergence – multiple target organs – fight or flight response explained Adrenal gland – modified cluster of postganglionic cell bodies that release epinephrine & norepinephrine into blood Anatomy of Parasympathetic NS Preganglionic cell bodies found in – 4 cranial nerve nuclei in brainstem – S2 to S4 spinal cord Postganglionic cell bodies very near or in the wall of the target organ in a terminal ganglia  Parasympathetic Cranial Nerves Oculomotor nerve – ciliary ganglion in orbit – ciliary muscle & pupillary constrictor muscle inside eyeball Facial nerve – pterygopalatine and submandibular ganglions – supply tears, salivary & nasal secretions Glossopharyngeal – otic ganglion supplies parotid salivary gland Vagus nerve – many branchess supply heart, pulmonary and GI tract as far as the midpoint of the colon  Parasympathetic Sacral Nerve Fibers Form pelvic splanchnic nerves Preganglionic fibers end on terminal ganglia in walls of target organs Innervate smooth muscle and glands in colon, ureters, bladder & reproductive organs  ANS Neurotransmitters Classified as either cholinergic or adrenergic neurons based upon the neurotransmitter released Adrenergic Cholinergic  Cholinergic Neurons and Receptors Cholinergic neurons release acetylcholine from preganglionic neurons & from parasympathetic postganglionic neurons Excites or inhibits depending upon receptor type and organ involved Nicotinic receptors are found on dendrites & cell bodies of autonomic NS cells and at NMJ Muscarinic receptors are found on plasma membranes of all parasympathetic effectors  Adrenergic Neurons and Receptors Adrenergic neurons release norepinephrine (NE) ) – from postganglionic sympathetic neurons only – Excites or inhibits organs depending on receptors – Alpha1 and Beta1 receptors produce excitation – Alpha2 and Beta2 receptors cause inhibition – Beta3 receptors(brown fat) increase thermogenesis NE lingers at the synapse until enzymatically inactivated by monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT)  Physiological Effects of the ANS Most body organs receive dual innervation – innervation by both sympathetic & parasympathetic Hypothalamus regulates balance (tone) between sympathetic and parasympathetic activity levels Some organs have only sympathetic innervation – sweat glands, adrenal medulla, arrector pili mm & many blood vessels – controlled by regulation of the “tone” of the sympathetic system  Sympathetic Responses Dominance by the sympathetic system is caused by physical or emotional stress -- “E situations” – emergency, embarrassment, excitement, exercise Alarm reaction = flight or fight response – dilation of pupils – increase of heart rate, force of contraction & BP – decrease in blood flow to nonessential organs – increase in blood flow to skeletal & cardiac muscle – airways dilate & respiratory rate increases – blood glucose level increase Long lasting due to lingering of NE in synaptic gap and release of norepinephrine by the adrenal gland  Parasympathetic Responses Enhance “rest-and-digest” activities Mechanisms that help conserve and restore body energy during times of rest Normally dominate over sympathetic impulses SLUDD type responses = salivation, lacrimation, urination, digestion & defecation and 3 “decreases”--- decreased HR, diameter of airways and diameter of pupil Paradoxical fear when there is no escape route or no way to win – causes massive activation of parasympathetic division – loss of control over urination and defecation  Autonomic or Visceral Reflexes Autonomic reflexes occur over autonomic reflex arcs. Components of that reflex arc: – sensory receptor – sensory neuron – integrating center – pre & postganglionic motor neurons – visceral effectors Unconscious sensations and responses – changes in blood pressure, digestive functions etc – filling & emptying of bladder or defecation  Control of Autonomic NS Not aware of autonomic responses because control center is in lower regions of the brain Hypothalamus is major control center – input: emotions and visceral sensory information smell, taste, temperature, osmolarity of blood, etc – output: to nuclei in brainstem and spinal cord – posterior & lateral portions control sympathetic NS increase heart rate, inhibition GI tract, increase temperature – anterior & medial portions control parasympathetic NS decrease in heart rate, lower blood pressure, increased GI tract secretion and mobility