Chapter 21: Nerve Cells

 

 

Neuron/Nervous System Structure:

·      Neuronal structure (21-1) – The three types of neurons are sensory, interneurons and motor; parts of a neuron and their functions; synapses are points of communication between neurons (21-4).

·      Neuronal circuits – knee jerk reflex circuit (21-5); nervous system organization (21-6).

 

The Action Potential:

·      Membrane potential – measurement (21-7); types of ion channels involved in electrical activity of neurons (21-8); resting ion concentrations and calculating membrane potential (21-9); effect of ion permeability on membrane potential (21-10).

·      Membrane depolarization – passive spread of ions entering the cell; time course of opening voltage gated cation channels (21-12); mechanisms of channel opening (21-13); unidirectional movement of the action potential without loss of strength (21-14); depolarization is dependent on ion concentrations at the membrane rather than wholesale changes in ion concentration; myelin structure and impact on neuronal function (21-17).

 

Properties of Voltage-gated Channels:

·      How to measure individual channel function – patch clamping (20-19); affect of altering current (ion) flux on membrane potential (21-21).

·      Structure and mechanism of action (21-24) – P segment determines ion selectivity; S4 transmembrane domain acts as the voltage sensor; N-terminal ball causes the channel to assume an inactive state (21-26); voltage gated channels for different ions have similar structures (21-27).

 

Neurotransmitters and Synaptic Signaling:

·      Types of neurotransmitters – except for acetylcholine are either amino acids or derived from amino acids (21-28).

·      Storage and release of neurotransmitters – stored in regulated secretory vesicles; depolarization of the membrane causes an influx of Ca⁺² ions through V-gated Ca⁺² channels; Ca⁺² bind to synaptotagmin, which triggers membrane fusion and secretion of neurotransmitter; endocytosis then regenerates the vesicles, which are filled with neurotransmitter via H⁺ antiporter then dock with proteins at the plasma membrane (21-29, 21-31).

·      Excitatory and inhibitory synapses (21-32)– opening Na⁺ or Na⁺ and K⁺ Channels leads to excitation of the cell due to membrane depolarization; opening K⁺ or Cl^- channels leads to inhibition due to membrane hyperpolarization.

·      Fast and slow synapses – synapses can transmit information at different speeds; in fast synapses (0.1-2 milliseconds), ligand gated receptors on the post-synaptic cell are themselves ion channels which open in response to neurotransmitter (T21-1); if the neurotransmitter binds to an excitatory receptor which is a Na⁺ channel, the membrane will be depolarized; If the neurotransmitter binds to an inhibitory receptor and opens a Cl^- channel, the membrane will be hyperpolarized; slow synapses (seconds to minutes) generally have G protein coupled receptors on the post-synaptic cell (T21-2); Once activated, post-synaptic G protein coupled receptors can activate a G protein that in turn activates an ion channel or activates second messenger pathways.

·      Transmitters can activate multiple receptors – acetylcholine can activate nicotinic and muscarinic acetylcholine receptors; nicotinic receptors are  fast and excitatory while muscarinic are slow and can be excitatory or inhibitory; acetylcholine is the neurotransmitter at the neuromuscular junction.

·      Acetylcholine signaling is terminated by acetylcholinesterase, which is present in large amounts in the synaptic cleft and hydrolyzes acetylcholine; the choline produced by acetylcholinesterase is taken up by the pre-synaptic cell and used to generate more acetylcholine; other neurotransmitters are recycled via reuptake by the axon terminals that released them.

·      Chemical and electrical synapses – chemical synapses enable the properties of amplification and computation; an impulse can be amplified since relatively few neurotransmitter molecules can lead to muscle contraction; axons from different cells synapse at dendrites of a post-synaptic cell and a action potential will only be generated if the small depolarizations at each synapse reach the threshold potential (21-34); gap junctions are present at electrical synapses and lead to near instantaneous transmission of the action potential from pre- to post-synaptic cell since ions can move through gap junctions.

 

Neurotransmitter Receptors:

·      Acetylcholine-gated cation channels – activation of nicotinic acetylcholine receptors leads to a muscle contraction; the opening of cation channels leads to a large influx of Na⁺, depolarization of the membrane, release of Ca⁺² from the sarcoplasmic reticulum and a muscle contraction (21-37); Release of acetylcholine from a single vesicle, or a quanta, causes a small depolariztion far below the threshold potential.

·      ACH receptor structure (21-38) – composed of five subunits; junctions between aand d and a and g are where two acetylcholines bind to activate; M2 helices line the pore and have negatively charged residues that let cations through; acetylcholine binding causes a conformational change that opens the channel.

·      Glutamate-gated cation channels (21-40) – activation of a post-synaptic neuron makes it more sensitive to subsequent stimulation, which is a simple form of learning; this is controlled by NMDA and non-NMDA glutamate receptors; NMDA receptors are coincidence detectors since they only open if the cell is partly depolarized and glutamate is bound, thus it takes fewer action potentials to in presynaptic neurons to cause a response in the post-synaptic neuron; partial depolarization causes the release of Mg⁺² ion that blocks the NMDA receptor.

·      Inhibitory channels – GABA and Glycine gated Cl^- channels cause a hyperpolarization of the post-synaptic cell; although Cl^- channels have a similar structure to Na⁺/K⁺ channels, they have positively charged amino acids at either end of the M2 helix.

·      Muscarinic ACH receptors – bind to acetylcholine, activate a G protein which then activates a K⁺ channel; the activated K⁺ channel causes a hyperpolarization of the membrane and is therefore inhibitory.

·      Adrenergic receptors – are all G protein coupled receptors that lead to the activation of ion channels that either depolarize or hyperpolarize the membrane depending on the cell type.

·      Facilitation – serotonin leads to increased cAMP levels, which shut down K⁺ channels in the axon terminus; closing of K⁺ channels make it take longer for repolarization and prolonged neurotransmitter secretion (21-42).

·      Neuropeptides – can function as neurotransmitters; activate G protein coupled receptors; are kept separate from the CNS by the blood-brain barrier.

 

Sensory Transduction:

·      Mechanoreceptors/salt receptors – mechanoreceptors are Na⁺ or Na⁺/Ca⁺² channels that are activated by touch or stretching; salt receptors are ungated Na⁺ channels and are activated by high Na⁺ concentration; capsaicin from chili peppers activates Na⁺/Ca⁺² channels that are on pain neurons and also open when heated.

·      Vision – controlled by rod and cone photoreceptors; cones control color perception and rods are more sensitive to light; rods contain rhodopsin, which are the light sensitive protein (21-44); photoreceptors are constantly depolarized at –30mV and release neurotransmitter; when light is absorbed the cell hyperpolarizes and decreases NT release (21-45).

·      Light absorption (21-46) – rhodopsin is an opsin G protein coupled receptor that is bound to 11-cis-retinal; light changes the 11-cis-retinal to all-trans-retinal, causing a conformational change and activation of G_t (transducin).

·      cGMP and hyperpolarization (21-47) – transducin activates cGMP phophodiesterase, which hydrolyzes cGMP and reduces the activation of cGMP gated Na⁺/Ca⁺² channels.

·      Visual adaptation – it takes some time to adapt to a dark room or bright light; adaptation is controlled by a low Ca⁺² induced increase in the synthesis of cGMP in low light and high Ca⁺²/calmodulin induced binding to and opening of cGMP gated channels in high light; adaptation also occurs by phosphorylation, where phosphorylation of opsin decreases its ability to activate transducin and thus cGMP-gated channels, and more light is needed to cause a hyperpolarization; arrestin can also bind to opsin and block its ability to activate transducin in high light.

·      Color vision – controlled by opsins that absorb red, blue or green light in cone cells (21-49); light detection mechanism is the same as for rhodopsin; red and green opsins are next to each other on the X chromosome and removal of one by unequal crossing over leads to red/green colorblindness.

·      Olfaction (21-50)– a thousand different G protein coupled receptors on sensory neurons in the nose are used to detect the millions of chemicals that we encounter in the environment; each neuron expresses a different receptor, but all neurons use the G_olf G protein to activate the second messenger pathway; all neurons that detect a single odorant synapse on a specific group of interneurons in the olfactory bulb, which then relay these signals to other parts of the brain.

 

Learning and Memory:

·      Memory – long term memory last days to years and requires gene expression that alters neuronal connections; short term memory lasts for minutes to hours and is controlled by altering the release of neurotransmitter or receptivity to neurotransmitter.

·      Forms of learning – habituation is a decrease in response due to a repeated stimulus that has no adverse effect; sensitization is the increase in response due to a adverse stimulus; classical conditioning is the association of one event (the CS) with a later reinforcing event (the US).

·      Gill withdrawl – touching the siphon will cause the gill to withdraw by means of a simple neuronal circuit (21-52); touching the siphon 10-15 times causes habituation because there is a decrease in the amount of glutamate release due to a decrease in the amount of V-gated Ca⁺² channels; if siphon touching is followed by a blow to the head, this will increase the speed of gill withdrawal (sensitization) due to increased glutamate release; increased glutamate release is due to a facilitator neuron (serotonin, cAMP, etc.).

·      Classical conditioning – training in Aplysia is a weak touch to the siphon (CS) and a blow to the head (US), which leads to an increased gill withdrawal upon a weak siphon touch; mechanism underlying classical conditioning (21-53).

·      Long term memory – if time elapses between training sessions for classical conditioning, then the task will be remembered long-term; the additional time is required for gene expression leading to restructuring of neuronal connections.