Neuronal nuclei protein

When the creation of long-term memories— repeated stimulations interrupted by rest periods—was simulated in this preparation by repeated pulses of serotonin, anatomical changes occurred. Specifically, new synaptic connections were created. It is likely that there are two underlying components to formation of new synaptic connections. One is local protein synthesis in the nerve terminal and the other is CREB (cAMP response element binding) dependent transcription in the neuronal nucleus. Of course, serotoiun pulses also stimulated the release of glutamate. So now the question is how repeated pulses of serotonin are related to protein synthesis and formation of new synapses. 

Cyclic AMP has been implicated in synaptic transmission due to its actions on a number of important synaptic and neuronal events, such as membrane permeability, synaptic membrane phosphorylation, neurotransmitter synthesis, and cell growth and differentiation. As pointed out earlier, neurotransmitter-receptor interactions can result in direct physical perturbations of the membrane with consequent alterations in membrane permeability to specific ions. This effect is particularly the case when the ionophore is located near the receptor. However, if the ionic channel is distant from the receptor, mechanisms such as phosphorylation can result in an alteration of channel permeability. Cyclic AMP is known to lead to a hyperpolarization of neurons in a number of brain regions such as the cerebral cortex, the caudate nucleus, the peripheral paravertebral sympathetic ganglia, the cerebellar cortex, and the hippocampus. Although it has been hypothesized that this hyperpolarization is the consequence of the phosphorylation of specific neuronal membrane proteins, the relatively short duration of hyperpolarization... 

Maroteaux L, CampaneUi JT, Scheller RH. Synudein a neuron-specific protein localized to the nucleus and presynaptic nerve terminal. / Neurosci. 1988 8(8) 2804—2815. 

Like other cells, a neuron has a nucleus with genetic DNA, although nerve cells cannot divide (replicate) after maturity, and a prominent nucleolus for ribosome synthesis. There are also mitochondria for energy supply as well as a smooth and a rough endoplasmic reticulum for lipid and protein synthesis, and a Golgi apparatus. These are all in a fluid cytosol (cytoplasm), containing enzymes for cell metabolism and NT synthesis and which is surrounded by a phospholipid plasma membrane, impermeable to ions and water-soluble substances. In order to cross the membrane, substances either have to be very lipid soluble or transported by special carrier proteins. It is also the site for NT receptors and the various ion channels important in the control of neuronal excitability. 

Certainly the activity of tyrosine hydroxylase is greater in the DA neurons of the substantia nigra (17.5 nmol dopa synthesised/mg protein/h) than in the NA neurons of the locus coeruleus (4-5), as is the turnover of the amine itself (1.7 pg/h) compared with that of NA (1.0) (see Bacopoulus and Bhatnager 1977). In the caudate nucleus and nucleus accumbens the turnover of DA is even higher at 7.4 and 2-6 pg/g/h respectively. 

Second, although typical neuroleptics produce depolarisation block of both A9 and AlO neurons, the atypical neuroleptics only induce it in AlO neurons (Chiodi and Bunney 1983). So after an atypical neuroleptic the A9 neurons of the nigrostriatal tract remain functional, which would explain why EPSs are not seen. Another difference is seen with the expression of an immediate-early gene, c-fos, and although its functional significance is not clear, typical neuroleptics induce its protein production in both the striatum and nucleus accumbens while the atypicals only achieve it in the accumbens. 

FIGURE 26-8 Immunohistochemical localization of cAMP response element-binding protein (CREB) in rat hippocampal neurons. Using a polyclonal antibody which recognizes both CREB and phospho-CREB protein, it is apparent that CREB protein is enriched in the nucleus of pyramidal cells of the CA1 region of the hippocampus. Scale bar is 30 pm. (Courtesy of Dr Stephen Ginsberg, Department of Pathology, University of Pennsylvania.)... 

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