Neuroscience
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To determine the sensitivity of basal forebrain cholinergic neurons to ionotropic glutamate receptor activation, acetylcholine was collected from the cerebral cortex of urethane-anesthetized rats using microdialysis while monitoring cortical electroencephalographic (EEG) activity. alpha-Amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA; 1, 10, or 100 microM), N-methyl-D-aspartate (NMDA; 100 or 1000 microM) or a combination of AMPA (10 microM) and NMDA (100 microM) was administered to the basal forebrain using reverse microdialysis. Both glutamate receptor agonists produced concentration-dependent, several-fold increases in acetylcholine release indicating that they activated basal forebrain cholinergic neurons; AMPA was more potent, increasing acetylcholine release at a lower concentration than NMDA. The combination of AMPA and NMDA did not produce any greater release than each drug alone, indicating that the effects of these two drugs on cholinergic neurons are not additive. ⋯ The highest concentrations of AMPA and NMDA tested produced small (25%) but significant increases in high frequency activity. There was a positive correlation across animals between the increases in power in the beta (14-30 Hz) and gamma (30-58 Hz) ranges and increases in acetylcholine release. These results indicate that glutamate can activate cholinergic basal forebrain neurons via both AMPA and NMDA ionotropic receptors but has a more modest effect on EEG activation.
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Neurons of the principal nucleus of the bed nuclei of the stria terminalis (BSTp) process pheromonal and viscerosensory stimuli associated with reproduction and relay this information to preoptic and hypothalamic cell groups that regulate reproductive function. The anteroventral periventricular nucleus of the hypothalamus (AVPV), a nucleus involved in the regulation of gonadotropin secretory patterns, receives dense projections from BSTp neurons in males but not in females. ⋯ Treatment of newborn females with testosterone or neonatal orchidectomy of males reversed these sex differences, while GAD65-immunoreactivity in the AVPV was not altered in response to exogenous hormone treatments administered to peripubertal animals. Our results suggest that projections from BSTp neurons constitute a stable, sex-specific GABAergic input to the AVPV that is patterned permanently by perinatal hormone exposure.
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Cholinergic disturbances have been implicated in schizophrenia. In a recent study we found that intracerebroventricular (i.c.v.) delivery of the immunotoxin 192 IgG-saporin, that effectively destroys cholinergic projections from the basal forebrain to hippocampus and cortex cerebri, leads to a marked facilitation of amphetamine-induced locomotor activity in adult rats. The aim of the present experiments was to evaluate the contribution of the septohippocampal versus the basalocortical cholinergic projections for the amphetamine hyper-response seen previously in i.c.v. 192 IgG-saporin injected rats. ⋯ Possible effects of these three lesions on spontaneous and amphetamine-induced locomotor activity were assessed in locomotor activity cages. We find that selective cholinergic denervation of cortex cerebri, but not denervation of hippocampus or damage to cerebellum can elicit dopaminergic hyper-reactivity similar to that seen in previous i.c.v. 192 IgG-saporin experiments. Our data are compatible with the hypothesis that disturbances of cholinergic neurotransmission in cortex cerebri may be causally involved in forms of schizophrenia.
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This study investigated the relationship between the orexins and patterns of activity in the diurnal Nile grass rat, Arvicanthis niloticus. Some individuals of this species switch to a more nocturnal pattern when given access to a running wheel, while others continue to be most active during the day. In both day- and night-active grass rats, the percentages of orexin A (OXA) and orexin B (OXB) cells expressing Fos were highest when animals were actively running in wheels. ⋯ This study demonstrates that individual differences in the patterns of activation of OXA and OXB cell populations are related to differences in the temporal pattern of wheel running. We also present evidence that orexin cells have projections to the intergeniculate leaflet that appear to make contact with neuropeptide-Y cells. We discuss the possibility that these fibers may be involved in relaying feedback regarding the activity state of the animal to the circadian system through these projections.
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Psychostimulants and antipsychotic drugs increase mRNA expression of the neuropeptide neurotensin (NT) in the striatum and nucleus accumbens. In the present study, we used mice lacking the dopamine transporter (DAT) to investigate the consequences of a chronic hyperdopaminergic state on NT gene expression. NT mRNA expression was examined under basal conditions and after administration of haloperidol or amphetamine using in situ hybridization with a digoxigenin-labeled NT cRNA probe. ⋯ Amphetamine (10 mg/kg) increased the number of hybridized neurons in the nucleus accumbens shell and fundus striati of wild-type and DAT-/- mice, indicating that the drug acted through a target other than DAT, such as the serotonin or the norepinephrine transporters. The up-regulation of NT mRNA observed in DAT-/- mice may represent an adaptive mechanism in response to constitutive hyperdopaminergia. These results illustrate the profound alterations in the NT system induced by chronic stimulation of DA receptors and underscore the potential clinical relevance of NT/DA interactions in schizophrenia and drug abuse.