New Sensory 1 Nagy Nervous System PDF

# NERVOUS SYSTEM ## Organization of Nervous System - Histological - **Neurones** - Basic unit - Human CNS: 10^11 neurones - Each neurone: 2000 synapses - 2 x 10^14 synapses - **Glial cells (Neuroglia)** - Supporting cells - 10-50 times number o...

# NERVOUS SYSTEM ## Organization of Nervous System - Histological - **Neurones** - Basic unit - Human CNS: 10^11 neurones - Each neurone: 2000 synapses - 2 x 10^14 synapses - **Glial cells (Neuroglia)** - Supporting cells - 10-50 times number of neurones - 3 types: - **Microglial:** phagocytic cells - **Oligodendrites:** Myelin sheath - **Astrocytes:** Maintain K+ & BBB - Anatomical and Functional - **CNS** - **Higher brain (cortical level)** - Fine motor & sensory - Thinking, memory, learning, speech - **Lower brain (subcortical level)** - Subconscious activities - CVS, respiration, GIT control - Posture & equilibrium - Emotional reactions, wakefulness - **Spinal Cord Level** - Immediate autonomic activities - Withdrawal reflexes - Walking movement, support reactions - Bladder and rectal evacuation. - **PNS** - **Sensory (Afferents)** - **Motor (Efferents)** - **Somatic** to skeletal muscle. - **Autonomic** to exocrine glands, endocrine glands, cardiac muscle, smooth muscle. ## Synapses - **Definition:** Site of junction between 2 neurones. Axon terminal of presynaptic & postsynaptic. - **Transmission** - **Electric:** Gap junction, rare. Short latency. - **Chemical:** Chemical transmitter, long latency. Common, controllable, one way. - **Types of Synapses:** - **Axo-dendritic (80-98%)** - least excitable - **Axo-somatic** - **Axo-exonic** - Most excitable. Lowest threshold, more voltage gated Na+ channels. Site of generation of AP. Adjacent to axon hillock, spreads forwards and backwards. - **Functions** - Not simple transmission, but complex. - **Allow Grading and Adjustment** - Facilitating transmission. - Amplification of transmission. - Blocking. - Changing on repeated stimuli. - Distribution of information. - Integration of information. - Storage of information. ## Functional Anatomy - **Synaptic Knobs** - Terminal Boutons. - **Synaptic Cleft:** 20-40 nm. Post synaptic density. - **Vesicles** - **Small clear:** ACh, Glycine, GABA, Glutamate. Short term (ms or less), formed in cell body. - **Small dense:** Catecholamines. Near synaptic cleft, small holes release via exocytosis. - **Large (dense) granular:** Neuropeptides. Long term (min, h, days or more). All parts of presynaptic terminal. Small amount, not recycled. - **Notes:** One neurone usually secretes ONE type of chemical transmitter. Excitation or inhibition depends on the receptor. ## Functions of Dendrites: 1. Expand area of integration. 2. Some innitiate AP. 3. Dendritic spines appear, disappear, or change in min or h; important for motivation, learning, and long-term memory. ## Mechanism of Synaptic Transmission 1. **Release:** AP opens voltage-gated Ca++ channels, leading to: - Migration of vesicles to active zone. - Fusion of V-SNARE and t-SNARE. - Release if ch.tr by process of exocytosis, which is dependent on Ca++. 2. **Binding:** Ch. transmiter binds to a specific receptor (ionotropic or metabotropic). 3. **Generation of:** - **EPSP (Fast):** Na+ influx - **IPSP (Slow):** Cl-influx - **GPSP (Fast):** K+ efflux. 4. **Inactivation** - **Presynaptic:** Active reuptake. - **Cleft:** Diffuse away in ECF. - **Postsynaptic:** Inactivation. - **Microglia:** Removal. ## EPSP/IPSP - **EPSP:** Depolarizing - **Transient**, localized, partial. - **Fast or slow**. - **Opening** of Na+ channels (mainly) and Ca++ channels. - **Characters:** Graded, summed, spatial - **Space:** Many simultaneously. - **Length constant** depends on number of knobs - **IPSP:** Hyperpolarizing - **Fast**. - **Opening** of Cl- channels (mainly) and K+ channels (slow IPSP). - **Time:** Begins 0.5 msec. Peak 11.5 msec, lasts 15 msec. - **Characters:** graded, summed, temporal. - **Time:** One repetitively. - **Time constant** depends on frequency of stimulus. - **Notes:** Slow postsynaptic potential lasts several seconds. - **Site:** autonomic ganglia, cortical neurones, smooth muscle, cardiac muscle. - **Latency:** 100-500 ms. - **Slow EPSP:** K+ conductance decreases. - **Slow IPSP:** K+ conductance increase. ## GPSP - Notes: Algebraic sum of EPSP and IPSP at one neurone. Results in: Inhibition, excitation, AP, or no changes. In a motor neurone, the axon hillock is most excitable (lowest threshold), and it's likely to fire in both directions: - **Down the axon:** Antrograde. - **Back to the soma:** Retrograde to wipe out electrical activity of the cell for new activity. ### Example: Micturition - **Supraspinal centers:** Facilitatory and inhibitory pathways. ## Presynaptic Facilitation - 3rd neurone is excitatory. - Metabotropic, slow. - Axo-axonic. - **Notes:** - Protein kinase A phosphorylates proteins of the K+ channel. - Closure of the K+ channels. - **Consequences:** - Prolonged depolarization. - Delay in repolarization. - Prolongs the opening of Ca++ channels. - Increase release of chemical transmitter. ## Presynaptic Inhibition - 3rd neurone is inhibitory. - Metabotropic. - Axo-axonic. - **Notes:** - 2+ efflux (from presynaptic cell) & Cl- conductance. - Direct influence of selective signaling to the postsynaptic cell. - Not directly related to Ca++, but to the release of the chemical transmitter. ## Characters of Synaptic Transmission 1. **Forwards Direction:** From PRE (presynaptic cell) to POST (postsynaptic cell). 2. **Synaptic Delay:** 0.5 msecond. - The central delay is a sum of the delays at all synapses. - 0.5 for the number of synapses minus the number of interneurones. - 1 for the number of synapses. 3. **Fatigue:** A rapid, repeated stimulus to the presynaptic or postsynaptic cell leads to: - Exhaustion of the chemical transmitter. - Inactivation of the receptor. - The importance is to prevent overexcitation of the CNS, which can lead to an epileptic fit. 4. **Synaptic Plasticity:** Ability to change (strengthened or weakened) over time, according to demands. Based on past experience. - **Short-term:** - Inhibition of habituation. - Post-tetanic potentiation. - Sensitization. - **Long-term:** - Potentiation (LTP). - Depression. - **Discuss:** The role of the presynaptic stimulus and postsynaptic response, the ionic bases of the mechanism, example, importance. ## Factors Affecting Synaptic Transmission - **Composition of Internal Environment:** - **Alkalosis:** Convulsion due to increased Ca++. Example: hyperventilation. - **Acidosis:** Coma due to increased Ca++. Example: DM. - **Hypoxia:** 3-5 second coma, prolonged brain damage. - **Hypoglycemia:** Coma, as brain fuel is only glucose. - **Hypocalcemia:** Tetany (too little Ca++) ## Drugs and Diseases - **Neurotoxins:** - **Drugs:** Theophylline, theobromine, caffeine. - **Diseases:** Tetanus toxins. - **Notes:** - Blocks the release of GABA and Glycine, leading to spastic paralysis (muscle spasms). - Symptoms include: clenched jaw (lockjaw), arched back, and prevented tetany. There is a toxoid vaccine. - **Botulism Toxins:** - **Notes:** - Blocks release of ACh. - Leads to flaccid paralysis. - Symptoms include: ptosis, diplopia, dysarthria (difficulty speaking), dysphagia (difficulty swallowing), and fatality is 5-10%. - There is an antitoxin. - Therapeutic uses of Botox include: facial muscles to remove wrinkles and achalasia of the esophagus. ## Short-Term Changes in Synaptic Transmission - **Short-term Inhibition (Habituation):** - A benign or neutral stimulus is repeatedly applied. - **Posttetanic Potentiation (PTP):** - A brief, high-frequency stimulation. - **Postsynaptic response** is prolonged and augmented. - **Ionic basis:** - **Ca++ pump** is weakened. - **Ca++ channels** are inactivated. - **Release of ch. transmitter** is increased. - **Important:** contributes to discharge for a few seconds or minutes after the stimulus. - **Sensitization:** - **Noxious stimulus** is applied. - **Mild benign stimulus** is also applied. - **Ionic basis:** - **Increased Ca++** influx. - **Presynaptic facilitation** of the chemical transmitter. - **Important:** contributes to learning and memory. - **Short-term memory:** Immediate memory is related to the changes in chemical transmitter concentrations. ## Long-Term Changes - **Long-term Potentiation (LTP):** - **Persistent strengthening of synaptic connections**. - **Ionic basis:** - **Glutamate** is released from presynaptic neurones. - **Glutamate** binds to AMPA and NMDA receptors on the postsynaptic membrane. - **Activation of AMPA receptors** leads to depolarization of the postsynaptic cell. - This depolarization removes the Mg block on the NMDA receptors and allows Ca++ to enter. - **Ca++ activates calmodulin** and calcium-calmodulin kinase II (CaM kinase II). - **CaM kinase II phosphorylates AMPA receptors**, increasing their conductance to Na+ and making the postsynaptic cell more responsive. - **CaM kinase II also moves more AMPA receptors** into the synaptic membrane. - **Importance:** underlies learning and memory. - **Long-term Depression:** - **Persistent weakening of synaptic connections**. - **Ionic basis:** - **Ca++** enters via NMDA receptors. - **Activation of AMPA receptors** in the postsynaptic membrane. - **Importance:** helps regulate the strength of synaptic connections. - **Key molecules:** AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors, NMDA (N-methyl-D-aspartate) receptors. - **Important note:** - **PTP:** short-term potentiation. - **LTP:** long-term potentiation. - **Ca++** in the presynaptic & postsynaptic cells are vital.