Excitability, neuronal, modulation

The objective of this chapter is to present the biophysical basis for electrical stimulation of neurons in the CNSs. The focus is on using fundamental understanding of both the electric field and its effects on neurons to determine the site of neuronal excitation or modulation in the CNS where electrodes are placed among heterogeneous populations of neuronal elements including cells, axons, and dendrites. 

Figure 15.9 Peptide modulation of striatal input to the globus pollidus. Enkephalin released from axon terminals of neurons of the indirect pathway (see Fig. 15.2 for details) is thought to inhibit GABA release from the same terminals so that feedback (auto) inhibition is reduced. This will free the neurons to inhibit the subthalamic nucleus (SThN) and its drive to GPint and SNr which in turn will have less inhibitory effect on cortico-thalamic traffic and possibly reduce akinesia. Dynorphin released from terminals of neurons of the direct pathway may also reduce glutamate release and excitation in the internal globus pallidus and further depress its inhibition of the cortico-thalamic pathway. High concentrations of these peptides may, however, result in dyskinesias. (See Henry and Brotchie 1996 and Maneuf et al. 1995)...

Noradrenaline acts on three types of receptor. The ai receptors mediate the main excitatory effects of noradrenaline upon wake-active neurons in the dorsal raphe, basal forebrain, and elsewhere (Vandermaelen Aghajanian, 1983 Nicoll, 1988 Fort et al., 1995 Brown et al., 2002). The a2 receptors mediate inhibitory effects of noradrenaline, e.g. on noradrenaline neurons themselves and on cholinergic brainstem neurons (Williams et al., 1985 Williams Reiner, 1993). The (3-receptors modulate neurons in a more subtle fashion, increasing excitability via blockade of afterhyperpolarizations in hippocampal and cortical neurons (Haas Konnerth, 1983). Activation of (3-receptors also promotes synaptic plasticity via activation of the cyclic-AMP-dependent kinase (PKA) and cyclic AMP response element binding protein (CREB) signal transduction pathway (Stanton Sarvey, 1987 Cirelli et al., 1996). 

McCarley, R. W. Hobson, J. A. (1975). Neuronal excitability modulation over the sleep cycle a structural and mathematical model. Science 189, 58-60. 

Nicola S., Surmeier J., Malenka R. (2000). Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens. A. Rev. Neurosci. 23,... 

Burdakov, D., Gerasimenko, 0. Verkhratsky, A. (2005). Physiological changes in glucose differentially modulate the excitability of hypothalamic melaninconcentrating hormone and orexin neurons in situ. J. Neurosci. 25,... 

As for the GABAa receptor, positive modulators that enhance glycine receptor activity have been identified. These include alcohols, neurosteroids, tropeines and the divalent metal ion Zn2+, which is highly enriched in some types of excitatory neuron [27], Zn2+ release from such neurons may potentiate glycine receptors at neighboring inhibitory synapses and thus facilitate inhibition following strong excitation. 

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