Excitatory input

Such clear postsynaptic potentials can be recorded intracellularly with microelectrodes in large quiescent neurons after appropriate activation but may be somewhat artificial. In practice a neuron receives a large number of excitatory and inhibitory inputs and its bombardment by mixed inputs means that its potential is continuously changing and may only move towards the threshold for depolarisation if inhibition fails or is overcome by a sudden increase in excitatory input. 

Figure 1.6 Presynaptic inhibition of the form seen in the dorsal horn of the spinal cord, (a) The axon terminal (i) of a local neuron is shown making an axo-axonal contact with a primary afferent excitatory input (ii). (b) A schematic enlargement of the synapse, (c) Depolarisation of the afferent terminal (ii) at its normal resting potential by an arriving action potential leads to the optimal release of neurotransmitter, (d) When the afferent terminal (ii) is already partially depolarised by the neurotransmitter released onto it by (i) the arriving acting potential releases less transmitter and so the input is less effective...

Figure 17.5 Possible scheme for the initiation of depolarisation block of DA neurons. In (a) the excitatory effect of glutamate released on to the DA neuron from the afferent input is counteracted by the inhibitory effect of DA, presumed to be released from dendrites, acting on D2 autoreceptors. In the absence of such inhibition due to the presence of a typical neuroleptic (b) the neuron will fire more frequently and eventually become depolarised. At5q)ical neuroleptics, like clozapine, will be less likely to produce the depolarisation of A9 neurons because they are generally weaker D2 antagonists and so will reduce the DA inhibition much less allowing it to counteract the excitatory input. Additionally some of them have antimuscarinic activity and will block the excitatory effect of ACh released from intrinsic neurons (see Fig. 17.7)...

As previously mentioned, a single action potential at a single synapse results in a graded potential only an EPSP or an IPSP. Therefore, generation of an action potential in the postsynaptic neuron requires the addition or summation of a sufficient number of excitatory inputs to depolarize this neuron to threshold. Two types of summation may occur ... 

As with temporal summation, this example has been simplified to illustrate the concept clearly. In actuality, a large number of excitatory inputs from different presynaptic neurons are necessary to depolarize the postsynaptic neuron to threshold. Because a typical neuronal cell body receives thousands of presynaptic inputs, spatial summation also occurs quite readily. The number of presynaptic neurons that are active simultaneously therefore influences the strength of the signal to the postsynaptic neuron. Under normal physiological conditions, temporal summation and spatial summation may occur concurrently. 

Figure 5.3 Spatial summation. Multiple excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials (IPSPs) produced by many presynaptic neurons simultaneously may add together to alter the membrane potential of the postsynaptic neuron. Sufficient excitatory input (A and B) will depolarize the membrane to threshold and generate an action potential. The simultaneous arrival of excitatory and inhibitory inputs (A and C) may cancel each other out so that the membrane potential does not change.

Altered release. Tetanus is an infectious disease caused by the bacterium Clostridium tetani. This bacterium produces a neurotoxin active on inhibitory synapses in the spinal cord. Motor neurons, which supply skeletal muscle and cause contraction, have cell bodies that lie in the spinal cord. Under normal circumstances, these motor neurons receive excitatory and inhibitory inputs from various sources. The balance of these inputs results in the appropriate degree of muscle tone or muscle contraction. Tetanus toxin prevents the release of gamma amino butyric acid (GABA), an important neurotransmitter active at these inhibitory synapses. Eliminating inhibitory inputs results in unchecked or unmodulated excitatory input to the motor neurons. The resulting uncontrolled muscle spasms initially occur in the muscles of the jaw, giving rise to the expression lockjaw. The muscle spasms eventually... 

An increase in arterial PC02 results in marked stimulation of the central chemoreceptors. In fact, this is the most important factor in regulation of ventilation. It is well known that it is impossible to hold one s breath indefinitely. As carbon dioxide accumulates in the arterial blood, the excitatory input to the respiratory center from the central chemoreceptors overrides the voluntary inhibitory input and breathing resumes. Furthermore, this occurs well before the arterial P02 falls low enough to stimulate the peripheral chemoreceptors. 

Conversely, a decrease in the arterial PCOz due to hyperventilation results in a decrease in the H+ ion concentration in the ECF of the brain. Decreased stimulation of the central chemoreceptors (and therefore a decrease in the excitatory input to the medullary respiratory center) causes... 

The osmoreceptors of the hypothalamus monitor the osmolarity of extracellular fluid. These receptors are stimulated primarily by an increase in plasma osmolarity they then provide excitatory inputs to the thirst center and the ADH-secreting cells in the hypothalamus. The stimulation of the thirst center leads to increased fluid intake. The stimulation of the ADH-secreting cells leads to release of ADH from the neurohypophysis and, ultimately, an increase in reabsorption of water from the kidneys and a decrease in urine output. These effects increase the water content of the body and dilute the plasma back toward normal. Plasma osmolarity is the major stimulus for thirst and ADH secretion two additional stimuli include ... 

A more moderate stimulus for thirst and ADH secretion is a decrease in extracellular fluid, or plasma volume. This stimulus involves low-pressure receptors in the atria of the heart as well as baroreceptors in the large arteries. A decrease in plasma volume leads to a decrease in atrial filling, which is detected by low-pressure receptors, and a decrease in MAP, which the baroreceptors detect. Each of these receptors then provides excitatory inputs to the thirst center and to the ADH-secreting cells. 

Tanaka, J., Nishimura, J., Kimura, F. Nomura, M. (1992). Noradrenergic excitatory inputs to median preoptic neurons in rats. Neuroreport 3, 95-106. 

Luetje CW, Patrick J (1991) Both alpha- and beta-subunits contribute to the agonist sensitivity of neuronal nicotinic acetylchohne receptors. J Neurosci 11 837-845 MameU-EngvaU M, Evrard A, Pons S, Maskos U, Svensson TH, Changeux JP, Faure P (2006) Hierarchical control of dopamine neuron-firing patterns by nicotinic receptors. Neuron 50 911-921 Mansvelder HD, McGehee DS (2000) Long-term potentiation of excitatory inputs to brain reward areas by nicotine. Neuron 27 349-357... 

Mansvelder HD, McGehee DS (2000) Long-term potentiation of excitatory inputs to brain reward areas by nicotine. Neuron 27 349-357... 

In addition to the physiological process of autoinhibition, another mechanism of presynaptic inhibition has been identified in the peripheral nervous system, although its precise relevance to the brain is unclear. In the dorsal horn of the spinal cord, for example, the axon terminal of a local neuron makes axo-axonal contact with a primary afferent excitatory input, which leads to a reduction in the neurotransmitter released. This is due to the local neuron partly depolarizing the nerve terminal, so that when the axon potential arrives, the change induced is diminished, thereby leading to a smaller quantity of transmitter being released. In the brain, it is possible that GABA can cause presynaptic inhibition in this way. 

Most cells normally receive a large excitatory input with a more or less constant generation of action potentials. The net result of generated IPSPs will be to decrease the number of nerve impulses per unit of time. By these mechanisms, neurotransmitters producing ei-... 

---