Excitatory pathways

Although subpopulations of mossy fibers may be peptidergic or cholinergic (see Sections 

Data from physiological studies including recent patch-clamp studies are in line with the assumption that glutamate is the neurotransmitter of mossy fibers (Garthwaite and Brodbelt, 1989, 1990 Silver et al., 1992 D Angelo et al., 1993 Rossi et al., 1995). 

Several observations have led to the assumption that L-aspartate is the principal neurotransmitter of climbing fibers. (1) Destruction of the inferior olive in the rat with 

Immunocytochemical studies have shown that subpopulations of climbing fibers may use peptides as a neurotransmitter, including somatostatine, corticotrophin-releasing factor and enkephalin. Their distribution and characteristics will be discussed in Section 

---

In the mammalian CNS powerful inhibitory systems function continually to slow the number of action potentials generated. The effects of stimulating an excitatory pathway can appear to be exaggerated if normal inhibitory influences to that region are diminished. Correspondingly, an inhibitory pathway will appear exaggerated if part of the excitatory influence to that system has been removed. 

When an excitatory pathway is stimulated, a small depolarization or excitatory postsynaptic potential (EPSP) is recorded. This potential is due to the excitatory transmitter acting on an ionotropic receptor, causing an increase in cation permeability. Changing the stimulus intensity to the pathway, and therefore the number of presynaptic fibers activated, results in a graded change in the size of the depolarization. When a sufficient number of excitatory fibers are activated, the excitatory postsynaptic potential depolarizes the postsynaptic cell to threshold, and an all-or-none action potential is generated. 

Interaction of excitatory and inhibitory synapses. On the left, a suprathreshold stimulus is given to an excitatory pathway (E) and an action potential is evoked. On the right, this same stimulus is given shortly after activating an inhibitory pathway (I), which results in an inhibitory postsynaptic potential (IPSP) that prevents the excitatory potential from reaching threshold. 

Excitatory synaptic potentials and spike generation. The figure shows a resting membrane potential of-70 mV in a postsynaptic cell. Stimulation of an excitatory pathway (E) generates transient depolarization. Increasing the stimulus strength (second E) increases the size of the depolarization, so that the threshold for spike generation is reached. 

Neurotransmitters can be classified as excitatory or inhibitory, depending on the nature of the action they elicit. Stimulation of excitatory neurons causes a movement of ions that results in a depolarization of the postsynaptic membrane. These excitatory postsynaptic potentials (EPSP) are generated by the following (1) Stimulation of an excitatory neuron causes the release of neurotransmitter molecules, such as norepinephrine or acetylcholine, which bind to receptors on the postsynaptic cell membrane. This causes a transient increase in the permeability of sodium (Na+) ions. (2) The influx of Na+ causes a weak depolarization or excitatory postsynaptic potential (EPSP). (3) If the number of excitatory fibers stimulated increases, more excitatory neurotransmitter is released, finally causing the EPSP depolarization of the postsynaptic cell to pass a threshold, and an all-or-none action potential is generated. [Note The generation of a nerve impulse typically reflects the activation of synaptic receptors by thousands of excitatory neurotransmitter molecules released from many nerve fibers.] (See Figure 8.2 for an example of an excitatory pathway.)... 

Invention Significance L-Glutamate mediates the excitatory pathway of... 

Electron microscopical immunogold studies have shown that Glu is enriched in nerve terminals in several excitatory pathways in the brain (Somogyi et al., 1986 Bramham et al., 1990 Maxwell et al., 1990, 1993 Broman and Ottersen, 1992 Walberg and Ottersen, 1992 ... 

Nicoll, R.A. (1970) Recurrent excitatory pathways of anterior commisure and mitral cell axons in the olfactory bulb. Brain Res., 19, 491 93. 

The mechanism of action of intravenous anaesthetics is thought to be by enhancement of inhibitory pathways or inhibition of excitatory pathways in the brain. Enhancement of the actions of GABA or inhibition at glutamate receptors seems most important, although modulation of other receptors may play a role as well. 

Central nervous system changes are the most frequently observed systemic toxicities of lidocaine. The initial manifestations are restlessness, vertigo, tinnitus, slurred speech, and eventually, seizures. Subsequent manifestations include CNS depression with a cessation of convulsions and the onset of unconsciousness and respiratory depression or cardiac arrest. This biphasic effect occurs because local anesthetics initially block the inhibitory GABAergic pathways, resulting in stimulation, and eventually block both inhibitory and excitatory pathways... 

The NMDA hypothesis, called the glutamatergic dysfunction hypothesis, of schizophrenia is based on the action of glutamate on NMDA receptors on GABAergic, serotonergic, and noradrenergic neurons that inhibit two major excitatory pathways in the retrosplenial cortical neurons. (Coyle, 1996). 

Engel, J., Jr., Henry, T.R., and Swartz, B.E. 1995. Positron emission tomography in frontal lobe epUepsy. Adv Neurol 66 223-238 discussion 238-241 Esclapez, M., Hirsch, J.C., Ben-Ari, Y, and Berntud, C. 1999. Newly formed excitatory pathways provide a substrate for hyperexcitability in experimenttil temporal lobe epUepsy. J Comp Neurol 408(4) 449-d60... 

Nadler, j. V., 1980, Role of excitatory pathways in the hippocampal damage produced by kainic acid, in Glutamate as a Neurotransmitter (G. DiChiara and G. L. Gessa, eds.), pp. 395-402, Raven Press, New York. 

Nadler, J. V., and Cuthbertson, G. J., 1980, Kainic acid neurotoxicity toward hippocampal formation dependence on specific excitatory pathways. Brain Res. 195 47-56. 

---