Neuroscience
-
Modulation of sympathetic drive to the spleen is one potential mechanism whereby physical activity prevents stress-induced splenic immune suppression in rats. The current study tested the hypothesis that voluntary freewheel running reduces peripheral sympathetic drive by modulating stress-induced activity of brain regions synaptically linked to sympathetically innervated peripheral organs, including the adrenals and spleen. To this end, adrenal and splenic catecholamine content and activity of the central sympathetic circuit indexed by c-Fos protein induction, elicited by acute exposure to inescapable tail shock, were measured. ⋯ Indicative of attenuated sympathetic drive to the spleen, however, 6 weeks of voluntary freewheel running diminished stress-induced splenic norepinephrine depletion, and significantly attenuated stress-induced c-Fos in specific brain regions responsible for sympathetic regulation, including tyrosine hydroxylase-immunoreactive neurons of the locus coeruleus, A5 cell group and rostral ventrolateral medulla. Results suggest that voluntary activity attenuates sympathetic drive to the spleen during stressor exposure by selectively modulating stress-induced activity of the central sympathetic circuit. The attenuation of sympathetic responses observed in this study may be one important mechanism for the protective effect of physical activity against stress-related illness and immunosuppression.
-
The amygdaloid complex has long been implicated in seizure disorders. Yet, projection cells of the lateral amygdaloid nucleus (LA) display little spontaneous activity suggesting that this seizure prone structure is normally controlled by strong inhibitory mechanisms. This control is achieved in part by local interneurons; however, a synaptically activated, Ca(2+)-dependent K(+) (K(Ca)) conductance has recently been identified as a second major inhibitory mechanism. ⋯ Charybdotoxin and isoproterenol produced positive shifts in the reversal potential, whereas apamin did not. By contrast, all three substances decreased adaptation during spike trains elicited by depolarizing current injections. These results suggest that intermediate (IK) and small (SK) conductance K(Ca) channels limit LA projection cell excitability, with IK channels involved in controlling both the synaptic response and intrinsic excitability of these neurons, and SK channels being involved only in the latter.
-
A control circuit is proposed to model the command of saccadic eye movements. Its wiring is deduced from a mathematical constraint, i.e. the necessity, for motor orders processing, to compute an approximate inverse function of the bio-mechanical function of the moving plant, here the bio-mechanics of the eye. This wiring is comparable to the anatomy of the cerebellar pathways. ⋯ The novelty of this model of movement control is that its structure is entirely deduced from mathematical and physical constraints, and is consistent with general anatomy, cell connectivity and functioning of the cerebellar pathways. Even the learning rules can be deduced from calculation, and they reproduce long term depression, the learning process which takes place in the dendritic arborization of the Purkinje cells. This approach, based on the laws of mathematics and physics, appears thus as an efficient way of understanding signal processing in the motor system.
-
Intermittent hypoxia (IH) during sleep, a characteristic feature of sleep-disordered breathing (SDB) is associated with time-dependent apoptosis and spatial learning deficits in the adult rat. The mechanisms underlying such neurocognitive deficits remain unclear. Activation of the cAMP-response element binding protein (CREB) transcription factor mediates critical components of neuronal survival and memory consolidation in mammals. ⋯ Initial IH-induced impairments in spatial learning were followed by partial functional recovery starting at 14 days of IH exposure. We postulate that IH elicits time-dependent changes in CREB phosphorylation and nuclear binding that may account for decreased neuronal survival and spatial learning deficits in the adult rat. We suggest that CREB changes play an important role in the neurocognitive morbidity of SDB patients.
-
Comparative Study
Differential psychostimulant-induced activation of neural circuits in dopamine transporter knockout and wild type mice.
Dopamine (DA) is a neurotransmitter that has been implicated in a wide variety of psychiatric disorders that include attention deficit-hyperactivity disorder (ADHD), schizophrenia, and drug abuse. Recently, we have been working with a mouse in which the gene for the DA transporter (DAT) has been disrupted. This mouse is hyperactive in the open field, displays an inability to inhibit ongoing behaviors, and is deficient on learning and memory tasks. ⋯ Since the DAT gene is disrupted in the KO mouse, these findings suggest that dopaminergic mechanisms may mediate the WT responses, whereas non-dopaminergic systems predominate in the mutant. In the mutants, it appears that limbic areas and non-dopaminergic transmitter systems within these brain regions may mediate responses to psychostimulants. Inasmuch as the KO mouse may represent a useful animal model for ADHD and because psychostimulants such as cocaine are reinforcing to these animals, our results may provide some useful insights into the neural mechanisms-other than DA-that may contribute to the symptoms of ADHD and/or drug abuse in human patients.