Neurophysiology I (1).pdf

NEUROPHYSIOLGY/ Introduction I Department Of Physiology 2nd stage MUHSIN ALNAJIM CONSUSLTANT IN NEUROLOGY  Nervous system divided in two major systems: 1.Central nervous system CNS; A. Brain (encephalon) I. Cerebrum: (2 cerebr...

NEUROPHYSIOLGY/ Introduction I Department Of Physiology 2nd stage MUHSIN ALNAJIM CONSUSLTANT IN NEUROLOGY  Nervous system divided in two major systems: 1.Central nervous system CNS; A. Brain (encephalon) I. Cerebrum: (2 cerebral hemispheres) a. Cerebral cortex(grey matter) , b. white matter c. basal ganglia d. Lateral ventricles II. Diencephalon: (epithalamus, thalamus, hypothalamus, subthalamus.}… 3rd venrtricle III. Brainstem: a. midbrain (cerebral aqueduct) b. pons c. medulla oblangata IV. Cerebellum. 4th (ventricle) B. Spinal cord 2. Peripheral nervous system; A. Somatic sensory (general and special) motor B. Autonomic nervous system; sympathetic and parasympathetic. right cerebral hemisphere of the human brain Lateral view of the right cerebral hemisphere of the human brain, shown in situ within the skull. A number of convolutions (called gyri) and fissures (called sulci) in the surface define four lobes—the parietal, frontal, temporal, and occipital—that contain major functional areas of the brain. cerebellum; human brain Dissection of the left hemisphere of the human brain, showing the internal capsule and middle cerebellar peduncle. Neuron The neuron (>100 billion within the human brain) is the functional unit of the nervous system. Neuronal specificity, size and cell type vary greatly. The neuron is constituted by its nucleus, cytoplasm, neuronal membrane and cytoskeleton. Neurons are identified as excitable cells because they have the ability to be electrically excited resulting in the generation of action potentials. Other examples of excitable cells are skeletal, smooth, and cardiac muscle cells and secretory cells of the pancreas. Functional Zones of Neurons: 1. Dendrites: Extend from the cell body to receive incoming signals, process them, and send information to the soma (cell body). 2. Initial Segment: The starting part of the axon, where action potentials are generated. 3. Axon: A long, fibrous extension from the axon hillock (which connects the axon to the cell body) that transmits impulses to the nerve endings. 4. Nerve Endings (Presynaptic Terminals): End in synaptic knobs (or terminal boutons), where action potentials trigger the release of neurotransmitters stored in vesicles, which are synthesized in the cell body. Myelin Sheath: Many axons are covered in myelin, a protein-lipid complex that insulates the axon. In the PNS, Schwann cells wrap around the axon, forming the myelin sheath. The myelin does not cover the axon at the nodes of Ranvier, where the axon is unmyelinated and action potentials "jump" between these nodes for faster conduction Excitation & Conduction: A key feature of neurons is their excitable membrane, which allows them to respond to electrical, chemical, or mechanical stimuli. Neurons generate two types of potentials: Local (non-propagated) potentials like synaptic responses. Propagated action potentials, which are essential for communication in the nervous system. Action potentials are the primary method of signal transmission, traveling without loss of strength (constant amplitude and velocity). Conduction is a self-propagating process, where the signal moves continuously along the nerve. Membrane Potential Maintenance: Two key factors maintain membrane potential: Unequal ion distribution across the membrane (a concentration gradient). Membrane permeability to specific ions through channels or pores in the lipid bilayer. In neurons: K+ concentration is higher inside the cell. Na+ concentration is higher outside the cell. This concentration difference is maintained by the Na-K ATPase pump, which actively moves Na+ out and K+ in. Passive ion movement: K+ moves out of the cell when K+ channels are open. Na+ moves in when Na+ channels are open. At rest, the membrane is more permeable to K+ because there are more open K+ channels than Na+ channels. As a result, K+ concentration is the main determinant of the resting membrane potential, which is close to the equilibrium potential for K+. Resting Membrane Potential (RMP): The Resting Membrane Potential is the electrical difference across the plasma membrane of a living cell when it is not stimulated. RMP is always measured as the potential inside the cell compared to the outside. In neurons, the RMP is typically around –70 mV. Ion leaks (like Na+ and K+) would eventually disrupt this balance, but the Na+/K+ ATPase pump actively moves Na+ out and K+ in to maintain the correct ion gradients. Action Potential (AP): An electrochemical signal that allows the nerve to transmit impulses over a distance. Occurs when: – There’s a change in voltage across the cell membrane. – Ionic gradients and membrane permeability create the conditions for it. – A threshold level of stimulus is reached. The action potential is propagated without losing strength (amplitude) as it moves along the nerve. It follows the All-or-None law: it either happens fully or not at all. Neuronal Membranes: Contain two types of ion channels: Ligand-gated channels (open when a neurotransmitter or chemical binds to them). Voltage-gated channels (open in response to a change in electrical charge across the membrane). Ion Conductance: Conductance of an ion depends on: Permeability; how easily it can pass through the membrane. The electrical resistance of the membrane. Steps of Action Potential: 1. Resting State: The neuron is at rest, with no ion movement across the membrane. 2. Depolarizing Stimulus: 1. A stimulus causes some voltage-gated Na+ channels to open, allowing Na+ to enter the cell. 2. The membrane potential reaches threshold. 3. Rapid Depolarization: 1. More Na+ channels open, leading to further depolarization in a positive feedback loop. 2. This causes a rapid rise in membrane potential (upstroke). 4. Na+ Channels Inactivate: The membrane potential moves toward +60 mV (Na+ equilibrium potential) but doesn't reach it because the Na+ channels quickly inactivate. 5. Repolarization: 1. At the peak (overshoot), the membrane potential reverses. 2. Voltage-gated K+ channels open, allowing K+ to exit, causing repolarization. 3. K+ channels open more slowly and stay open longer than Na+ channels. 6. After-Hyperpolarization: The slow closure of K+ channels causes a brief period of hyperpolarization (membrane potential becomes more negative than resting). 7. Return to Resting State: The membrane potential returns to its resting level after the K+ channels close. Threshold Intensity: The minimum strength of a stimulus needed to trigger an action potential. Strength-Duration Relationship: Weak stimuli need a longer duration to trigger a response. Strong stimuli can trigger a response with a shorter duration. This relationship forms the strength-duration curve. Refractory Periods: Absolute Refractory Period: From the start of the action potential until about one-third of repolarization. No stimulus, no matter how strong, can trigger a response. Relative Refractory Period: After the absolute refractory period, during the final part of repolarization. A stronger than normal stimulus can trigger a response. All or None Principle: An action potential will only occur if the stimulus reaches the threshold level. If the stimulus is too weak (subthreshold), no action potential will be generated. Once the threshold is reached, the action potential will occur and its size will remain constant, even if the stimulus gets stronger. Slowly increasing stimuli may not trigger an action potential because the nerve can adapt to the gradual change. Conduction of the Action Potential: During an action potential, positive charges from surrounding areas flow into the region where the action potential is happening. This flow reduces the polarity of the membrane in front of the action potential, triggering a local response. When the firing threshold is reached, a new action potential is initiated, propagating the signal further. Conduction in Myelinated Axons: In myelinated axons, conduction relies on circular current flow. Myelin acts as an effective insulator, so current flows only at the gaps between myelin (called nodes of Ranvier). Depolarization "jumps" from one node to the next, a process known as saltatory conduction. Saltatory conduction is much faster, allowing myelinated axons to conduct signals up to 50 times faster than unmyelinated fibers. Clinical Notes: Decreased Na+ (sodium) outside the cell: Lowers the strength of the action potential but has minimal impact on the resting membrane potential. Increased K+ (potassium) outside the cell (Hyperkalemia): Lowers the threshold for action potential, making the neuron more excitable. Decreased K+ outside the cell (Hypokalemia): Hyperpolarizes the membrane (makes it more negative), reducing the likelihood of an action potential. Calcium (Ca2+) effects: Decreased Ca2+ (Hypocalcemia): Increases membrane excitability. Increased Ca2+ (Hypercalcemia): Decreases membrane excitability. Glial cells or Neuroglia: Are non-neuronal cells in the CNS and the PNS that do not produce electrical impulses. *In the CNS, glial cells include oligodendrocytes, astrocytes, ependymal cells, and microglia. *In the PNS, glial cells include Schwann cells and satellite cells. They have four main functions: 1. Surround neurons and hold them in place. 2. Supply nutrients and oxygen to neurons. 3. Insulate one neuron from another. 4. Destroy pathogens and remove dead neurons. They also play a role in neurotransmission and synaptic connections. The Blood Brain Barrier (BBB): is a multicellular vascular structure that separates the central nervous system (CNS) from the peripheral blood circulation. Neurotrophins: Neurotrophins are a family of proteins that play a key role in the growth, survival, development, and function of neurons in both the central nervous system (CNS) and the peripheral nervous system (PNS). Besides their role in neurons, neurotrophins also have important functions in the immune and reproductive systems. Axonal Injury and Regeneration: Peripheral nerve damage: can often be repaired. The axon degenerates beyond the injury, but the connective tissues of the distal part (distal stump) usually survive. Axonal sprouting begins from the proximal stump, growing toward the distal stump. This growth is guided by Schwann cells, which release growth-promoting factors that attract the axon to the distal stump. Inhibitory molecules in the surrounding tissue (perineurium) ensure that the regenerating axons grow along the correct path. Neurotrophins produced by the distal stump further promote axonal growth. When the regenerating axon reaches its target (e.g., a neuromuscular junction), a new functional connection is formed. This enables significant, though not complete, recovery. Fine motor control may be permanently affected if some motor neurons connect to the wrong motor fibers. Peripheral nerve regeneration is much more successful compared to central nerve pathways. CNS Axonal Injury and Regeneration: In the CNS, the proximal stump of a damaged axon can form short sprouts, but the distal stump rarely recovers, and damaged axons are unlikely to form new synapses. CNS neurons lack the growth-promoting chemicals necessary for regeneration. In fact, CNS myelin actively inhibits axonal growth. After a CNS injury, factors such as: Astrocytic proliferation Activation of microglia Scar formation Inflammation and Immune cell invasion create an environment that is unfavorable for regeneration. As a result, treatment for brain and spinal cord injuries focuses on rehabilitation rather than reversing nerve damage.