Neuroscience
-
Working memory dysfunction is a core component of schizophrenia, which likely contributes substantially to the pervasive and profound cognitive deficits observed in patients with this illness. Developments in functional imaging have facilitated the investigation of the neural basis of these cognitive deficits. A strong tradition within neuropsychology has been that circumscribed lesions provide observations which constrain theoretical models, and generate testable predictions on the basis of observed relationships between structural abnormalities and behavioral dysfunction. ⋯ Empirical studies in schizophrenia research are reviewed in relation to principles of normal brain function sub-serving working memory: the functional role of the lateral prefrontal cortex, physiological response capacity constraints, inter-regional functional integration, and compensatory adaptations. However, complex heterogeneous psychiatric disorders such as schizophrenia cannot be considered akin to a pure lesion model, and there are considerable methodological challenges in interpreting disruptions of working memory in psychiatric conditions, resulting from clinical, treatment and performance related confounds. The increasing use of psychopharmacological models of disease in healthy human subjects is therefore considered as an attempt to address, or to some extent circumvent these issues.
-
Several findings suggest that glucocorticoid hormones influence the propensity of an individual to develop cocaine abuse. These hormones activate two related transcription factors, the glucocorticoid receptor and the mineralocorticoid receptor. We have shown previously that mice carrying a mutation of the glucocorticoid receptor gene specifically in neural cells, glucocorticoid receptor knock-out in the brain, show a dramatic decrease in cocaine-induced self-administration and no behavioral sensitization to this drug, two experimental procedures considered relevant models of addiction. ⋯ However, cocaine-induced changes in the levels of these mRNAs were not modified in glucocorticoid receptor knock-out in the brain mice. In contrast, mutant mice showed altered response in mRNA levels of N-methyl-D-aspartate, GLUR5 and GLUR6 glutamate receptor subunits as well as of enkephalin following cocaine administration. These modifications may be associated to decrease of behavioral effects of cocaine observed in glucocorticoid receptor knock-out in the brain mice.
-
Repeated cocaine administration in rats can lead to sensitization as evidenced by an increased locomotor response to a subsequent exposure (challenge) dose of cocaine even after a drug-free period. Expression of the immediate early gene product, c-Fos, differs among distinct subregions of the nucleus accumbens shell. This would suggest that these subregions may be differentially involved in sensitization. ⋯ Repeated cocaine administration resulted in robust sensitization that was associated with more deltaFosB in the vertex, arch, and cone compared with saline-treated controls. As previously reported, c-Fos immunoreactivity was increased in the intermediate zone in cocaine-sensitized rats. deltaFosB was significantly elevated in rats that did not receive a cocaine challenge, attesting to the long half-life of this transcription factor. These results provide further evidence suggesting distinct anatomical neuroadaptations within the nucleus accumbens shell that may play a functional role in psychomotor-stimulant sensitization.
-
This study compares the improvement and generalization of arm motor performance after physical or mental training in a motor task requiring a speed-accuracy tradeoff. During the pre- and post-training sessions, 40 subjects pointed with their right arm as accurately and as fast as possible toward targets placed in the frontal plane. Arm movements were performed in two different workspaces called right and left paths. ⋯ Control groups did not exhibit any improvement. These findings put forward the idea that mental training facilitates motor learning and allows its partial transfer to nearby workspaces. They further suggest that motor prediction, a common process during both actual and imagined movements, is a fundamental operation for both sensorimotor control and learning.
-
Comparative Study
Effect of early isolation on signal transfer in the entorhinal cortex-dentate-hippocampal system.
Deprivation of socio-sensory interactions during early life impairs brain function in adulthood. In previous investigations we showed that early isolation severely affects neuron development in several structures of the hippocampal region, including the entorhinal cortex. In the present study we investigated the effects of early isolation on signal processing along the entorhinal cortex-dentate-CA3-CA1 system, a major memory circuit of the hippocampal region. ⋯ While the entorhinal cortex was moderately impaired, the dentate-hippocampal system was more severely affected. The impairment in the signal transfer along the entorhinal cortex-dentate gyrus-CA3-CA1 system was heavier in males, confirming the larger susceptibility of this sex to early experience. This work provides evidence that malfunctioning of a major hippocampal network may underlie the learning deficits induced by impoverished surroundings during early life.