Neuroscience

Membrane Potentials
Resting Membrane Potential The fluid inside cells has a different composition to the fluid surrounding them. o Extracellular fluid consists mainly of Na+ and Cl- ions. o Intracellular fluid consists mainly of K+ and various inorganic ions. Resting membrane potential (Vr) the potential difference (difference in voltage) across the membrane of unstimulated excitable cells. o Caused by the asymmetrical distribution of ions and the selective permeability of the plasma membrane. o The polarity of the resting potential is always negative on the inside of the cell. o In neurons, Vr ranges between -60mV and -80mV. Generation of resting potentials o Most of the resting potential arises because of the uneven distribution of K+ ions across the plasma membrane. o The intracellular fluid contains K+ ions, whose positive charges are completely balanced by an equal number of anions. o Cell membranes are quite permeable to K+ ions, but are impermeable to the much larger anions. o Because there are no K+ ions in the extracellular fluid, a concentration gradient exists for potassium across the cell membrane. o Hence, a diffusion force acts to drive K+ down this gradient (out of the cell). o As soon as K+ ions leave the intracellular compartment, an equivalent number of negative charges on anions are unmasked. o This creates an electric force, which attracts K+ ions and so acts in the opposite direction to the diffusion force. o Over time, the system will reach equilibrium where diffusion force = electrical force. o At equilibrium, there will be a small deficit of K+ ions on the inside of the cell and a corresponding excess on the outside of the cell a potential difference is created. Nernst equation allows for the calculation of the equilibrium potential from the concentration of an ion outside (Xo) and inside (Xi) the cell. o Action Potentials Action potential the short lasting change in electrical potential associated with the passage of an impulse along the membrane of an excitable cell (eg. neurons or muscle cells).

Generation of action potentials 1. A stimulus is received by the dendrites of a nerve cell. This causes the Na+ channels to open. Na ions enter the cell. If the opening is sufficient to drive the interior potential from -70 mV up to -55 mV, the process continues. 2. Having reached the action threshold, more Na+ channels open. The Na+ influx drives the interior of the cell membrane up to about +30 mV. This process is called depolarization. 3. The Na+ channels close and the K+ channels open. K ions leave the cell. Since the K+ channels are much slower to open, the depolarization has time to be completed. Having both Na+ and K+ channels open at the same time would drive the system toward neutrality and prevent the creation of the action potential. 4. With the K+ channels open, K+ ions flow down their concentration gradient, out of the cell, and the membrane potential begins to return to its rest potential. This process is called repolarization. 5. The repolarization typically overshoots the rest potential to about -90 mV. This is called hyperpolarization (refractory period). Hyperpolarization prevents the neuron from receiving another stimulus during this time. 6. After hyperpolarization, the Na+/K+ pump eventually brings the membrane back to its resting state of -70 mV, through active transport.

Properties of action potentials o Constant amplitude in a given cell, all action potentials have the same amplitude. The size of an action potential carries no information about the size of the stimulus that produced it. o Latency the time lag between the start of the stimulus and onset of the action potential. The stronger a stimulus, the quicker it depolarizes a membrane and so the shorter the latency. Hence, the action potential latency does carry information about the size of the stimulus. o Refractory period about 0.5-1.0ms into the spike of the action potential, neurons become completely resistant (refractory) to further stimulation. This limits firing frequency; the maximum number of action potentials a neuron can fire in a second. This means that action potentials can only be propagated in one direction. They cannot go the wrong way because the membrane just upstream of the active region is inexcitable.

Propagation of Action Potential The stimulus triggers an action potential in the cell membrane of the nerve cell, and that action potential provides the stimulus for a neighboring segment of the cell membrane. Speed of an action potential o Depends on the diameter of the axon the larger the axon diameter, the higher the conduction speed. o Depends on myelination of the axon myelinated axons allow for higher speeds of transmission that nonmyelinated axons. Myelination of the axon o Unmyelinated axons have voltage-gated sodium channels along the entire length of the membrane. In contrast, myelinated axons have voltage-gated sodium channels only in the Nodes of Ranvier.

o Action potential propagation along unmyelinated axons requires activation of voltage-gated sodium channels along the entire length of the axon. Action potential propagation along myelinated axons requires activation of voltage-gated sodium channels only in the nodal spaces. o Saltatory conduction the process by which action potentials jump between successive nodes.

Synapses and Neurotransmission

Synapse a junction between two nerve cells, consisting of a minute gap across which impulses pass by diffusion of a neurotransmitter. o Synaptic cleft a gap that separates the presynaptic and postsynaptic membranes. o Within the presynaptic terminal lie two types of synaptic vesicles that contain neurotransmitters. o The presynaptic membrane has an active zone where synaptic vesicles can dock and release neurotransmitters into the synaptic cleft. o The postsynaptic membrane directly opposite the active zone has a postsynaptic density packed with receptors capable of binding neurotransmitters. Neurotransmission the process by which neurotransmitters diffuse across the synapse, to initiate a response on the postsynaptic membrane. o Neurotransmission is an example of excitation-secretion coupling. Neurotransmitters chemical substances that are released at the end of a nerve fiber by the arrival of a nerve impulse and, by diffusing across the synapse or junction, cause the transfer of the impulse to another nerve fiber, a muscle fiber, or some other structure. o Characteristics of neurotransmitters The transmitter must be synthesized by the nerve. The transmitter must be released by the nerve. Postsynaptic receptors for the transmitter must exist. There should be an active mechanism for termination of activity of the transmitter. Sequence of events of neurotransmission 1. An action potential arrives at the presynaptic terminal. 2. Depolarization opens voltage-dependent calcium channels in the presynaptic membrane allowing Ca2+ to enter the terminal.

3. The influx and rise in Ca2+ concentration triggers the release of transmitter from a synaptic vesicle that has already docked at the active zone into the synaptic cleft. 4. The transmitter diffuses across the cleft, and binds to its receptors on the postsynaptic membrane. 5. Binding of transmitter and receptor alters the conductance of the postsynaptic potential (precisely which ions depends on the nature of the transmitter and on which of its receptors is involved). 6. Transmitter is transported back into the neuron. 7. The synaptic vesicle is recycled and reloaded with transmitter.

Neurotransmitter receptors o Ligand-gated ion channels (ionotropic receptors) transmembrane ion channels with neurotransmitter-binding sites on their extracellular face, which protrudes into the synaptic. Transmitter binding opens the channel, thus permitting ions to flow. This produces a postsynaptic current, which changes the membrane potential, generating a postsynaptic potential. o G-protein-coupled receptors (metabotropic receptors) modulate the activity of ion channels indirectly so transmission via these is slower. Purpose of synapses o Synaptic delay slows the transmission nerve signals. The more synapses there are in a neural pathway, the longer it takes information to get from its origin to its destination. o Chemical synapses are the decision-making devices of the nervous system. The more synapses a neuron has, the greater its informationprocessing capability.

Neural integration
Neural integration the ability of neurons to process, store and recall information, and make decisions. Postsynaptic potentials

o Excitatory postsynaptic potential (EPSP) when neurotransmission acts to increase the chance of an action potential being fired. If activation of a receptor causes a net inward current, the postsynaptic membrane depolarizes. This brings the cell closer to the threshold for firing action potentials. Usually caused by Na+ influx. Examples of excitatory neurotransmitters: glutamate, aspartate. o Inhibitory postsynaptic potential (IPSP) when neurotransmission acts to decrease the chance of an action potential being fired. If activation of a receptor produces a net outward current to flow through the postsynaptic membrane, the effect is to make the membrane potential more negative. This reduces the probability that the postsynaptic neuron will fire. Can be caused by a K+ efflux or Cl- influx. Examples of inhibitory neurotransmitters: glycine, aminobutyrate (GABA). Summation the process of adding up postsynaptic potentials and responding to their net effect. o A neuron may receive input from thousands of presynaptic neurons simultaneously; some may produce EPSPs while others produce IPSPs. o Whether or not the neuron fires depends on whether the net input is excitatory or inhibitory. o Two ways to overcome the problem that a single EPSP rarely ever causes a post-synaptic action potential alone: Temporal summation a single presynaptic neuron stimulates the postsynaptic neuron so intensely that its EPSPs add up to threshold and makes it fire. Spatial summation multiple inputs to the postsynaptic cell each produce a moderate amount of stimulation, but collectively they produce enough EPSPs to add up to threshold at the trigger zone and make the cell fire. Facilitation the process in which one neuron enhances the effects of another one. o One neuron acting alone may be unable to induce a postsynaptic neuron to fire. o But when multiple neurons cooperate, their combined effort does induce a postsynaptic neuron to fire. Presynaptic inhibition the process in which one presynaptic neuron suppresses the effect of another one (the opposite of facilitation). Neural coding the way in which the nervous system converts information to a meaningful patter of action potentials. o Qualitative information is encoded in terms of which neurons are firing.

A weak stimulus excites neurons with the lowest thresholds, while a strong stimulus excites less sensitive high-threshold neurons. o Quantitative information (information about the intensity of the stimulus) is encoded in two ways: Depending on the fact that different neurons have different thresholds of excitation. Depending on the fact that the more strongly a neuron is stimulated, the more frequently it fires. o Neural pools large ensembles which consist of thousands to millions of interneurons concerned with a particular body function. The functions of a neural pool are partly determined by its neuronal circuit the pathway among its neurons.

Organisation of the Spinal Cord

The Spinal Cord Functions of the spinal cord o Conduction The spinal cord contains bundles of nerve fibers that conduct information up and down the cord, enabling sensory information to reach the brain and motor command to reach the effectors. o Reflexes The spinal cord is the integrator of the system that coordinates involuntary stereotyped responses to stimuli. Gross anatomy of spinal cord o The spinal cord is a cylinder of nervous tissue that begins at the foramen magnum and passes through the vertebral canal as far as the inferior margin of the first lumen vertebra. o It occupies only the upper two-thirds of the vertebral column. o Divided into 4 regions based on the level of the vertebral column from which the spinal nerves emerge: Cervical region detect arm/neck sensations. Thoracic region detect chest/abdomen sensations Lumbar region detect upper leg sensations Sacral region detect lower leg sensations o The spinal cord is enlarged at 2 sites (cervical and lumbar regions) corresponding to the innervations of the upper and lower limbs. o Three fibrous membranes called meninges separate the soft tissue of the CNS from the bones of the vertebrae. From superficial to deep, they are the dura mater, arachnoid mater and pia mater. Internal structure of spinal cord o Grey matter has a relatively dull colour because it contains little myelin. In the middle of the spinal cord.

Contains the somas, dendrites and proximal parts of the axons of neurons. It is the site of synaptic contact between neurons. Consist of two dorsal horns and two thicker ventral horns. o White matter contains an abundance of myelinated axons, which give it a bright, pearly white appearance. Surrounds grey matter. Composed of bundles of axons celled tracts, which carry signals from one part of the CNS to another. Tracts are arranged in three pairs called columns: Dorsal column nerves are all afferent (come from the periphery into the brain) Lateral column Ventral column nerves are all efferent (come from the brain to the periphery)

Spinal Tracts Tracts are both structural and functional organizations of nerve fibers: o Structural All axons of any one tract originate from neuron cell bodies located in the same area of the CNS. All axons of any one tract terminate in a single structure elsewhere in the CNS.

o Functional All axons that compose one tract serve one general function. Ascending tracts conduct sensory impulses up to the brain. Descending tracts conduct motor impulses down the spinal cord.

Spinal Nerves There are 31 pairs of spinal nerves: o 8 cervical (C1-C8) o 12 thoracic (T1-T12) o 5 lumbar (L1-L5) o 6 sacral (S1-S5) The first cervical nerve emerges between the skull and the atlas, and the others emerge through intervertebral foramina (openings). Sensory nerve fibers enter the spinal cord via the dorsal roots and their accompanying cell bodies are located in the dorsal root ganglia. o Types of sensory nerve fibers: A myelinated (thick axon) Act as proprioceptors of skeletal muscle. A myelinated (thinner axon) Act as mechanoreceptors of skin. A myelinated (thin axon) Act as pain and temperature receptors. C non-myelinated (thinnest axon) Act as temperature, pain and itch receptors. o Thinner nerve fibers (A and C) synapse very superficially. Motor nerve fibers exit the spinal cord via the ventral root and their accompanying cell bodies are found in the ventral horn.

Spinal Reflexes
Overview of Reflexes Reflexes quick, involuntary, stereotyped reactions of glands or muscles to stimulation. o Reflexes require stimulation. They are not spontaneous actions but responses to sensory input. o Reflexes are quick. They generally involve few if any interneurons and minimum synaptic delay. o Reflexes are involuntary. They occur without intent, often without our awareness, and they are difficult to suppress. o Reflexes are stereotyped. They occur in essentially the same way every time; the response is very predictable. Types of reflexes:

o Monosynaptic reflexes with on interneurons, with only one synapse. o Disynaptic reflexes with one interneuron, with two synapses. o Polysynaptic reflexes with many interneurons. Reflex arc the pathway along which a signal travels to initiate a reflex. 1. Somatic receptors detect sensory input from the skin, muscle or tendon. 2. Afferent nerve fibers carry information from the receptors into the dorsal horn of the spinal cord. 3. Interneurons integrate information (lacking form some reflex arcs). 4. Efferent nerve fibers carry motor impulses to the skeletal muscles. 5. Skeletal muscles somatic effects that carry out the response.

Examples of Somatic Reflexes Stretch reflex mediates muscle contraction is response to stretching within the muscle, providing automatic regulation of skeletal muscle length. o At its simplest level, this is a negative feedback mechanism that defends muscle length. o Stretch reflexes smooth joint action and maintain equilibrium and posture. o Many stretch reflexes are monosynaptic so there is minimal synaptic delay and a very quick response. o A stretch reflex is often accompanied by reciprocal inhibition, a reflex that prevents an antagonistic muscle from contracting and interfering with the stretch reflex. o Muscle spindle sensory receptor within the belly of a muscle, which detects stretching (ie. changes in the length of the muscle).

Flexor reflex the withdrawal of a limb form an injurious stimulus, as in pulling back from a sharp object.

o Employs a polysynaptic reflex arc that produces a sustained response in muscle. Tendon reflex the inhibition of a muscle contraction that occurs when a tendon is excessively stretched. o The reflex prevents tendon injuries and helps to distribute workload across a muscle.