Physiology
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Organization of the Nervous System, Basic Functions of Synapses, Transmitter Substances
The central nervous system contains more than 100 billion neurons. figure shows a typical neuron of a type found in the brain motor cortex. Incoming signals enter this neuron through synapses located mostly on the neuronal dendrites, but also on the cell body. A special feature of most synapses is that the signal normally passes only in the forward direction (from the axon of a preceding neuron to dendrites on cell membranes of subsequent neurons). This forces the signal to travel in required directions for performing specific nervous functions
Sensory Part of the Nervous SystemSensory Receptors
Most activities of the nervous system are initiated by sensory experience exciting sensory receptors, whether visual receptors in the eyes, auditory receptors in the ears, tactile receptors on the surface of the body, or other kinds of receptors. This sensory experience can either cause immediate reaction from the brain, or memory of the experience can be stored in the brain for minutes, weeks, or years .Motor Part of the Nervous System-Effectors.
This is achieved by controlling (1) contraction of appropriate skeletal muscles throughout the body, (2)contraction of smooth muscle in the internal organs, and (3) secretion of active chemical substances by both exocrine and endocrine glands in many parts of the body. These activities are collectively called motor functions of the nervous system, and the muscles and glands are called effectors because they are the actual anatomical structures that perform the functions dictated by the nerve signals.
Role of Synapses in Processing Information.
The synapseA synapse: is the connection between the axon terminal of a presynaptic neuron and the dendrite of a postsynaptic neuron. The synapse contains vesicles that secrete chemicals known as neurotransmitters. Some of the more common neurotransmitters are acetylcholine, serotonin and dopamine. These neurotransmitters are necessary in the process of the action potential. Synaptic transmission can be affected by many types of drugs and disease processes.
Presynaptic Terminals.
Electron microscopic studies of the presynaptic terminals show that they have varied anatomical forms, but most resemble small round or oval knobs and, therefore, are sometimes called terminal knobs, buttons, end-feet, or synaptic knobs. showing a single presynaptic terminal on the membrane surface of a postsomatic neuron. The presynaptic terminal is separated from the postsynaptic neuronal soma by a synaptic cleft having a width usually of 200 to 300 angstroms. The terminal has two internal structures important to the excitatory or inhibitory function of the synapse: the transmitter vesicles and the mitochondria. The transmitter vesicles contain the transmitter substance that, when released into the synaptic cleft, either excites or inhibits the postsynaptic neuronexcites if the neuronal membrane contains excitatory receptors, inhibits if the membrane contains inhibitory receptors. The mitochondria provide adenosine triphosphate (ATP), which in turn supplies the energy for synthesizing new transmitter substance. When an action potential spreads over a presynaptic terminal, depolarization of its membrane causes a small number of vesicles to empty into the cleft. The released transmitter in turn causes an immediate change in permeability characteristics of the postsynaptic neuronal membrane, and this leads to excitation or inhibition of the postsynaptic neuron, depending on the neuronal receptor characteristics.
The nerve impulse
An action potential ( nerve impulse) is the movement or exchange of ions of sodium and potassium along the length of a nerve fiber resulting in a stimulus that activatesanother neuron or another tissue. Before a fiber can respond to a stimulus it must be polarized. A polarized fiber has an excess of sodium ions on the outside of the axon membrane, which produces a difference in electrical charge called the resting potential. When a stimulus of sufficient strength arrives at the receptor of the neuron, the polarized nerve becomes depolarized. Once depolarization happens, a sequence of ionic exchanges occur along the axon and the action potential is transmitted. After the axon membrane reaches maximum depolarization, the original concentrations of sodium and
potassium are reestablished in a process called repolarization. This restores the resting potential of the cell and it is ready to send another impulse. Action potentials travel in only one direction and are an all - or- none response. The speed of an action potential is determined by the diameter of the nerve fiber, its type(myelinated or nonmyelinated) and the condition of the neuron.
There are two major types of synapses:
(1) the chemical synapse(2) the electrical synapse. Almost all the synapses used for signal transmission in the central nervous system of the human being are chemical synapses. In these, the first neuron secretes at its nerve ending synapse a chemical substance called a neurotransmitter (or often called simply transmitter substance), and this transmitter in turn acts on receptor proteins in the membrane of the next neuron to excite the neuron, inhibit it, or modify its sensitivity in some other way. More than 40 important transmitter substances have been discovered . Some of the best known are acetylcholine, nor epinephrine, epinephrine, histamine, gamma-amino butyric acid (GABA), glycine, serotonin, and glutamate.
Electrical synapses, in contrast, are characterized by direct open fluid channels that conduct electricity from one cell to the next. Most of these consist of small protein tubular structures called gap junctions .
One-Way Conduction at Chemical Synapses.
Chemical synapses have important characteristics : 1- they always transmit the signals in one direction: that is, from the neuron that secretes the transmitter substance, called the presynaptic neuron, to the neuron on which the transmitter acts, called the postsynaptic neuron. This is the principle of one-way conduction at chemical synapses,
2-summation:-repeated or simultaneous stimulation of motor neurons with sub minimal stimuli exhibit the phenomenon of summation.
Action of the Transmitter Substance on the Postsynaptic Neuron-Function of Receptor Proteins
The membrane of the postsynaptic neuron contains large numbers of receptor protein The molecules of these receptors have two important components:
(1) a binding component that protrudes outward from the membrane into the synaptic clefthere it binds the neurotransmitter coming from the presynaptic terminal.
(2) an ionophore component that passes all the way through the postsynaptic membrane to the interior of the postsynaptic neuron. The ionophore in turn is one of two types: (1) an ion channel that allows passage of specified types of ions through the membrane or (2) a second messenger activator that is not an ion channel but instead is a molecule that protrudes into the cell cytoplasm and activates one or more substances inside the postsynaptic neuron. These substances in turn serve as second messengers to increase or decrease specific cellular functions.
Chemical Substances That Function as Synaptic Transmitters
More than 50 chemical substances have been proved or postulated to function as synaptic transmitters.. One group comprises small-molecule, rapidly acting transmitters. The other is made up of a large number of neuropeptides of much larger molecular size that are usually much more slowly acting.
The small-molecule, rapidly acting transmitters are the ones that cause most acute responses of the nervous system, such as transmission of sensory signals to the brain and of motor signals back to the muscles. The neuropeptides, in contrast, usually cause more prolonged actions, such as long-term changes in numbers of neuronal receptors, long-term opening or closure of certain ion channels, and possibly even long term changes in numbers of synapses or sizes of synapses.
Small-Molecule, Rapidly Acting Transmitters
Class I: Acetylcholine
Class II: The Amines , Nor epinephrine Histamine
Class III: Amino Acids , Gamma-amino butyric acid (GABA) ,
Glycine , Glutamate , Aspartate
Class IV: Nitric oxide (Nor epinephrine Dopamine Serotonin)
Small-Molecule, Rapidly Acting Transmitters
In most cases, the small-molecule types of transmitters are synthesized in the cytosol of the presynaptic terminal and are absorbed by means of active transport into the many transmitter vesicles in the terminal. Then, each time an action potential reaches the presynaptic terminal, a few vesicles at a time release their transmitter into the synaptic cleft. This usually occurs within a millisecond or less by the mechanism described earlier. The subsequent action of the small molecule type of transmitter on the membrane receptors of the postsynaptic neuron usually also occurs within another millisecond or less. Most often the effect is to increase or decrease conductance through ion channels; an example is to increase sodium conductance, which causes excitation, or to increase potassium or chloride conductance, which causes inhibition.
Neuropeptide, Slowly Acting Transmitters or Growth Factors
Pituitary peptides , Prolactin , β-Endorphin, Luteinizing hormone , Thyrotropin, Growth hormone , Vasopressin , Oxytocin , Leucine enkephalin , Gastrin
, Methionine enkephalin , Substance P , Cholecystokinin , Nerve growth factor
, Neurotensin , Insulin , Glucagon , From other tissues , Angiotensin II
, Bradykinin
Thyrotropin-releasing hormone
Hypothalamic-releasing hormones
α-Melanocyte-stimulating hormone
Brain-derived neurotropic factor
Vasoactive Intestinal Polypeptide (VIP)
Peptides that act on gut and brain
Luteinizing hormonereleasing hormone
Somatostatin (growth hormone inhibitory factor)
Adrenocorticotropic hormone (ACTH)
Neuropeptides
They are synthesized as integral parts of large-protein molecules by ribosomes in the neuronal cell body. The protein molecules then enter the spaces inside the endoplasmic reticulum of the cell body and subsequently inside the Golgi apparatus, where two changes occur: First, the neuropeptide-forming protein is enzymatically split into smaller fragments, some of which are either the neuropeptide itself or a precursor of it. Second, the Golgi apparatus packages the neuropeptide into minute transmitter vesicles that are released into the cytoplasm. Then the transmitter vesicles are transported all the way to the tips of the nerve fibers by axonal streaming of the axon cytoplasm, traveling at the slow rate of only a few centimeters per day. Finally, these vesicles release their transmitter at the neuronal terminals in response to action potentials in the same manner as for small-molecule transmitters. However, the vesicle is autolyzed and is not reused.
Because of this laborious method of forming the neuropeptides, much smaller quantities of them are usually released than of the small-molecule transmitters.
Effect of Acidosis or Alkalosis on Synaptic Transmission.
Most neurons are highly responsive to changes in pH of the surrounding interstitial fluids. Normally, alkalosis greatly increases neuronal excitability. For instance, a rise in arterial blood pH from the 7.4 norm to 7.8 to 8.0 often causes cerebral epileptic seizures because of increased excitability of some or all of the cerebral neurons. This can be demonstrated especially well by asking a person who is predisposed to epileptic seizures to over breathe. The over breathing blows off carbon dioxide and therefore elevates the pH of the blood momentarily, but even this short time can often precipitate an epileptic attack. Conversely, acidosis greatly depresses neuronal activity; a fall in pH from 7.4 to below 7.0 usually causes a comatose state. For instance, in very severe diabetic or uremic acidosis, coma virtually always develops.Effect of Hypoxia on Synaptic Transmission.
Neuronal excitability is also highly dependent on an adequate supply of oxygen. Cessation of oxygen for only a few seconds can cause complete in excitability of some neurons. This is observed when the brains blood flow is temporarily interrupted, because within 3 to 7 seconds, the person becomes unconscious.