Synapse
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Prenatal stress alters neuronal morphology of mesocorticolimbic structures such as frontal cortex and hippocampus in the adult offspring. We investigated here the effects of prenatal stress on the spine density and the dendrite morphology of hippocampal pyramidal neurons and medium spiny cells from nucleus accumbens in prepubertal and adult male offsprings. Sprague-Dawley pregnant dams were stressed by restraining movement daily for 2 hours from gestational day 11 until delivery. ⋯ Prenatally stressed animals demonstrated increased locomotion and alterations in spine density in the hippocampus and nucleus accumbens at both ages. However, prepubertal males showed an increase in spine density in the CA1 hippocampus with a decrease in CA3 hippocampus, whereas the adult group showed a decrease in the spine density in both of the regions studied. These results suggest that prenatal stress carried out during the middle of pregnancy affect the spine density and basal dendrites of pyramidal neurons of hippocampus, as well as the dendritic morphology of nucleus accumbens which may reflect important changes in the mesocorticolimbic dopaminergic transmission and behaviors associated with the development of psychiatric diseases such as schizophrenia.
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Propofol is now the most commonly used intravenous anesthetic-for general anesthesia and sedation because of its rapid onset and recovery. Besides the well-known adverse effects of cardiovascular and respiratory depression, recent studies indicate that propofol may cause excitatory phenomena such as myoclonus, opisthotonus, and even seizure. However, the mechanisms of these excitatory effects of propofol have not been elucidated. ⋯ Furthermore, protein kinase C (PKC) inhibition suppressed propofol-mediated facilitation of glutamate release. These results suggest that subanesthetic concentration propofol facilitates glutamate release from rat cerebrocortical glutamatergic terminals by increasing nerve terminal excitability, likely through the activation of PKC pathway. This finding may provide an explanation for propofol-induced excitatory phenomena.
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Hippocampal long-term potentiation (LTP) is suppressed not only by stress paradigms but also by low frequency stimulation (LFS) prior to LTP-inducing high frequency stimulation (HFS; tetanus), termed metaplasticity. These synaptic responses are dependent on N-methyl-D-aspartate receptors, leading to speculations about the possible relationship between metaplasticity and stress-induced LTP impairment. However, the functional significance of metaplasticity has been unclear. ⋯ Extracellular levels of gamma-aminobutyric acid (GABA), but not glutamate, in the hippocampus increased during exposure to CFC or LFS. Furthermore, electrical stimulation of the medial prefrontal cortex (mPFC), which caused decreases in freezing behavior during exposure to CFC, counteracted the LTP impairment induced by LFS. These findings suggest that metaplasticity in the rat hippocampal CA1 field is related to the neural basis of stress experience-dependent fear memory, and that hippocampal synaptic response associated stress-related processes is under mPFC regulation.
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Adrenergic agonists have different modulatory effects on excitatory synaptic transmission depending on the receptor subtypes involved. The present study examined the loci of alpha(1)- and beta-adrenoceptor agonists, which have opposite effects on excitatory neural transmission, involved in modulation of glutamatergic transmission in layer V pyramidal cells of rat cerebral cortex. Phenylephrine, an alpha(1)-adrenoceptor agonist, suppressed the amplitude of AMPA receptor-mediated excitatory postsynaptic currents evoked by repetitive electrical stimulation (eEPSCs, 10 pulses at 33 Hz). ⋯ Phenylephrine suppressed inward currents evoked by puff application of glutamate, AMPA, or NMDA, whereas isoproterenol application was not accompanied by significant changes in these inward currents. These findings suggest that phenylephrine decreases eEPSCs through postsynaptic AMPA or NMDA receptors, while the effects of isoproterenol are mediated by facilitation of glutamate release from presynaptic terminals without effect on postsynaptic glutamate receptors. These two different mechanisms of modulation of excitatory synaptic transmission may improve the "signal-to-noise ratio" in cerebral cortex.
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The mechanism by which deep brain stimulation (DBS) of the subthalamic nucleus (STN) achieves its effects in Parkinson's disease (PD) is not known. In animal models of PD, stimulation and lesioning of the STN have some effects which are the same, but others which differ, in reversing cellular and behavioral changes induced by dopamine depletion. We compared the effects of short-term STN stimulation and lesions upon extracellular levels of dopamine and metabolites using in vivo microdialysis of the dorsal striatum of awake, intact and unilateral 6-hydroxydopamine (6OHDA)-lesioned rats. ⋯ STN lesions of 6OHDA-lesioned rats did not affect relative metabolic ratios as compared with baseline levels. In 6-OHDA-lesioned rats, STN stimulation decreased extracellular levels of dopamine, and, to a greater extent, metabolites, resulting in a decrease in metabolic ratios. This further decrease in dopamine turnover with STN stimulation would serve to maintain dopamine levels in the dopamine-depleted striatum, and may account for the therapeutic benefit of DBS in Parkinson's disease.