Neuroscience
-
Regions of the prefrontal cortex that project to the nucleus accumbens in the rat receive input from midline thalamic and basal amygdaloid nuclei which also project to the same striatal region as their prefrontal cortical target. For example, the prelimbic cortex projects to the medial nucleus accumbens, and receives input from the paraventricular thalamic nucleus and the parvicellular basal amygdala. These latter two areas also project to the medial nucleus accumbens. ⋯ In the matrix of the core and the ventral part of the caudate-putamen, fibers from the superficial layers of the dorsal agranular insular area overlap precisely with afferents from the intermediodorsal nucleus. In the patches, projections from the deep layers of the dorsal agranular insular cortex coincide with those from the magnocellular basal amygdala. The present findings have implications for the compartmental structure of the nucleus accumbens and provide novel insights into the organizational principles of prefrontal corticostriatal circuits.
-
The effect of etomidate, an imidazole general anesthetic, on GABAA receptor function was studied in cultured hippocampal neurons. At a clinically relevant concentration of 4.1 microM, etomidate shifts the GABA dose response to the left (ED50 shift from 10.2 to 5.2 microM), with no change in the maximum current evoked by saturating concentrations of GABA. At a higher concentration of 82 microM, etomidate directly induces current in the absence of GABA. ⋯ Analysis of single channels opened by GABA indicates that 8.2 microM etomidate increases the probability of channels being open 13-fold and increases the effective channel open time two-fold. Given the present understanding of central inhibitory synapses, the effect of etomidate on channel kinetics is most likely to be the predominant mechanism which influences the synaptic function. In addition, etomidate, through its modulation of both channel kinetics and open probability, is likely to have a large impact on extrasynaptic GABAA receptor function.
-
The ventrobasal thalamus is the principal somatosensory thalamic relay nucleus, and it receives two major sources of excitatory input: firstly an input from ascending sensory afferents, and secondly a descending projection from the primary somatosensory cortex. There is considerable anatomical evidence to suggest that both of these projections utilise the excitatory amino acid L-glutamate as their neurotransmitter. Previous work from this laboratory has shown that the sensory input to the rat ventrobasal thalamus in vivo is mediated by ionotropic excitatory amino acid receptors of both the N-methyl-D-aspartate and non-N-methyl-D-aspartate type. ⋯ These data indicate that both N-methyl-D-aspartate receptors and Group I (possibly metabotropic glutamate receptors type I) metabotropic receptors are involved in the mediation of corticothalamic transmission. Such a transmitter mechanism would allow a modulatory system that could selectively enhance other excitatory inputs. Some of these data have been reported in abstract form.
-
The regional distribution of the serotonin uptake system was studied in rat brain using a specific polyclonal antibody raised against the putative extracellular loop between transmembrane domains 7 and 8 of the cloned rat serotonin transporter. Light microscope analysis with fluorescence and avidin-biotin-peroxidase techniques revealed a punctate staining as well as numerous labelled thin fibres, which exhibited accumulation of reaction end-product deposit over varicosities. These immunopositive processes were widely and heterogeneously distributed in the rat brain. ⋯ In addition, some immunoreactive fibres were present in the molecular and granular layers of the cerebellum as well as in the cochlear and olivary nuclei. In none of the regions analysed was evidence for glial staining obtained. The present immunocytochemical data reveal a widespread and heterogeneous distribution of the serotonin transporter in rat brain and suggest that serotoni transporter is preferentially sorted into axons, where it appears concentrated at varicosities and terminal boutons.
-
The expression of enkephalin and substance P messenger RNAs was examined in the caudate-putamen of human post mortem tissue from control and Huntington's disease tissue using in situ hybridization techniques and human specific enkephalin and substance P [35S] oligonucleotides. Macroscopic and microscopic quantification of enkephalin and substance P gene expression was carried out using computer-assisted image analysis. Tissue was collected from six control cases with no sign of neurological disease and six Huntington's disease cases ranging from grades 0 to 3 as determined by neuropathological evaluation. ⋯ For the early grade (0/1) Huntington's disease cases, a heterogeneous reduction in both enkephalin and substance P messenger RNAs were noted; for enkephalin messenger RNA the striatal autoradiograms displayed a conspicuous patchy appearance. Detailed cellular analysis of the dorsal caudate revealed a striking reduction in the number of enkephalin and substance P messenger RNA-positive cells detected and in the intensity of hybridization signal/cell. These data suggest that both the "indirect" GABA/enkephalin and "direct" GABA/substance P pathways are perturbed very early in the course of the disease and that these early changes in chemical signalling may possibly underlie the onset of clinical symptoms.