Neurophysiology

Neuron
A neuron is the basic element of the nervous system. It is composed of the main cell body (soma), which contains all the normal contents of cells, e.g. nucleus, Golgi apparatus etc. The neuron receives information from dendrites which are small branches leaving the soma. The neuron also sends information out via the axon, which begins at the axon hillock. These axons can be very short and thin or can be very long and thick. Some of the longest axons in the human body can extend from the motor cortex of the brain to the toe. In order to be able to transmit information over this distance axons are enclosed in a myelinated sheath composed of Shwann cells. Myelinated axons have breaks in them called nodes of Ranvier, which contain a very large number of voltage gated ion channels. At the terminal end of the axon there is a synapse which is where one neuron joins another neuron or muscle.

Resting membrane potential
The resting membrane potential of a cell measures the difference in charge on either side of the membrane. All cells have a resting membrane potential but only excitable cells, such as neurons, have a physiologically significant RMP. The RMP of a cell is dependant on the concentration of different ions inside and outside the cell, also the relative permeability of the membrane to these ions. This can be discovered by processing the Goldman equation. The RMP of a typical nerve cell is -70mV.

Action potential
Action potentials are the system that nerves use to transmit information over a long distance. Fundamentally, action potentials are a depolarisation of the membranes of excitable cells (such as neurons or muscle cells) and are an all or nothing response to a stimulus. Hodgkin and Huxley used a technique called voltage clamping in order to discover the ionic basis of the action potential. Their work lead to the sodium hypothesis which suggests that the initial depolarisation is caused by an influx of sodium through voltage gated sodium channels. An efflux of potassium through delayed voltage gated potassium channels causes the subsequent repolarisation and hyperpolarisation.

Synaptic potential
This is the wave of depolarisation or hyperpolarisation generated in the postsynaptic membrane following a presynaptic action potential. Synaptic potentials can either be excitatory postsynaptic potentials (EPSP's) or inhibitory postsynaptic potentials (IPSP's). EPSP's cause a depolarisation postsynaptically, while IPSP's cause a hyperpolarisation post synaptically. The nature of the synaptic potential depends on the transmitter released at the presynaptic membrane.

Synapse
A synapse is the terminal end of a neuron where it joins onto another neuron, a muscle, a receptor cell or other electrically excitable cells. As a synapse is a break between two cells electrical continuity is not possible, so a transmitter chemical is employed to continue the action potential. At the neuromuscular junction the transmitter chemical is acetylecholine (ACh), this is released from presynaptic vesicles, diffuses across the synapse, binds to ACh receptor sites. These sites are ligand gated ion channels that open to allow an influx of sodium thereby initiating an action potential post synaptically.

Peripheral nervous system
The peripheral (or somatic) nervous system is involved in bringing in somatic information to the brain about the position of the limbs in space. also in the control of skeletal muscles. It is composed of the nerves which lie outside the brain and spinal cord (the peripheral nerves) and the nerves which make up the ganglia. The peripheral nervous system innervates the skin, muscles and joints.

Autonomic nervous system
The parasympathetic (or autonomic) part of the nervous consists of the sympathetic nervous system, the parasympathetic nervous system and the enteric nervous system. The function of the autonomic nervous system is to regulate and control motor functions which we carry out 'automatically'. For example, breathing and control of smooth muscle. The sympathetic nervous system is involved in arousal and so expends energy. The parasympathetic nervous system however stores energy and helps to maintain the steady state of the body. Both the sympathetic and the parasympathetic systems use acetylecholine as their synaptic transmitter.

Hindbrain
The hindbrain is composed of the medulla oblongata, the pons and the cerebellum. The medulla oblongata lies just above the spinal cord and is involved in the regulation and initiation of autonomic functions such as digestion, breathing and heart rate. The pons are situated above the medulla and transmit motor information from the cerebral hemisphere to the cerebellum. The cerebellum itself lies behind the pons and connects to the brainstem by fibre tracts called peduncles. It is involved in coordinating the force and range of movements as well as playing a part in motor learning.

Midbrain
The midbrain (or mesencephalon) controls sensory and motor functions. It includes the control of eye movement along with visual and auditory reflexes. The midbrain contains two subdivisions, the tegmentum and the tectum. The tegmentum is made up of several nuclei, e.g. the reticular formation, grey matter, the red nucleus and the substantia nigra. The tectum is made up of the inferior colliculus and the superior colliculus.

Forebrain
The forebrain contains two major subdivisions, the diencephalon and the telencephalon. The diencephalon is made up of the hypothalamus and the thalamus. The hypothalamus lies under the thalamus and controls the autonomic nervous system and the endocrine nervous system. This is the hormonal system and so the hypothalamus is attached to a master endocrine gland, the pituitary gland. The thalamus is a relay for sensory pathways and makes up some of the input to the cortex. The telencephalon of the forebrain is made up of the basal ganglia and the cerebral cortex. The basal ganglia is involved in motor control. It co-ordinates and plans actions. Damage to the basal ganglia results in motor disorders such as those evident in Parkinson's disease.

Unimodal cortex
The primary neocortex is unimodal (i.e. of one mode). The input of the unimodal cortex is made up of one sensory modality and comes from the thalamus. The output of the unimodal cortex is to cortical areas of, again, the same modality.

Heteromodal cortex
The rest of the neocortex is heteromodal and so less specialised than the unimodal cortex. The input and the output of the heteromodal cortex is from and to other associated heteromodal regions.

Limbic system
The limbic system is made up of the paralimbic and the limbic cortices. This is the least specialised area of the cortex and some of the oldest; often it does not have the usual 6 layers of cortical cells. The limbic system is involved in learning and memory, emotion and new rewards. Olfactory information is also processed in the limbic area.

Cytoarchitecture
The cytoarchitecture of an organ like the brain refers to the pattern of the cells. In the cortex there are 6 layers of cells which vary in thickness depending on their position within the cortex. Looking at the cytoarchitecture of functionally different areas of the cortex allows us to guess at what cell layers are responsible for.

Acetylcholine
Aceylecholine (ACh) is a neurotransmitter secreted by efferent neurons. It is used as the transmitter at the neuromuscular junction and in the sympathetic and parasympathetic nervous system. ACh receptors are nicotinic and can be blocked by the antagonist curare. ACh is deactivated by acetylcholinesterase which cleaves ACh into acetate and choline. It is thought that ACh may play a role in memory.

Glutamate
Glutamate (or glutamic acid) is one of the main excitatory transmitters found in the brain. Its receptors are AMPA and kainite, this is itself a sodium channel. CNQX blocks the AMPA and kinate receptors (thereby acts as an antagonist). Kainic acid is however an agonist and acts by stimulating the kainite receptors. It is thought that Glutamate plays a role in learning, however, excessive activity may result in cell death and epilepsy.

GABA
GABA is one of the main inhibitory transmitters in the nervous system. Its receptors are GABAA, these are ionotropic Cl- channels and GABAB which is a metabotropic K+ channel. Bicuculline acts as a GABA agonist by blocking GABAA at GABA sites. Muscimol is an agonist of GABA and acts by stimulating GABAA at GABA sites. If there is an abnormally low quantity of GABA it may result in epilepsy.

Dopamine
Dopamine (DA) is both excitatory and inhibitory, depending on the postsynaptic receptor. There are in fact 4 types of these metabotropic receptors:
D1 = EPSP by raising the level of cyclic AMP (cAMP).
D2 = IPSP by lowering the level of cAMP.
D3&D4 = IPSP by again inhibiting cAMP.
Chlorpromazine in an antagonist and acts by blocking the D2 receptors. DA has three main circuits the neostriatal circuit, the mesolimbic circuit and the mesocortical circuit. Any decrease in DA in the neostriatal pathway results in Parkinson's disease, any increase in DA in the mesolimbic pathway results in schizophrenia.

Norepinephrine/Noradrenaline
Norepinephrine (NE) is very similar to dopamine in its pathways and actions. All of NE's receptors are metabotrophic, however the transmitter is not released from the terminals, but from axonal varicosities. Disipramine is an antagonist of NE and acts by inhibiting the postsynaptic uptake of NE. Phenylephrine acts as an agonist by stimulating the NE receptors. The circuits which use NE as a transmitter are found in the pons, the medulla, the locus coeruelus and the thalamus. It is thought that NE may play a role in attention.

Serotonin
Seratonin has 9 types of receptors which can be ionotropic or metabotropic. The transmitter is released from axonal varicosities not at the terminal. Fluoxetine (Prozac) inhibits 5HT re-uptake and so acts as an antagonist. LSD is an agonist and stimulates 5AT2A directly. The circuits which uses seritonin are in the raphe nuclei of the medulla, the pons and the midbrain.

Agonist/antagonist
Agonists and antagonists are drugs which interfere with brain activity. They can be agonists which facilitate activity e.g. kainic is an agonist of glutamate. Antagonists are drugs which inhibit activity e.g. curare inhibits ACh. Both types of drugs act by impacting upon transport, release, binding or re-uptake of a neurotransmitter.