Nature neuroscience
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Nature neuroscience · Oct 2007
Neurometabolic coupling in cerebral cortex reflects synaptic more than spiking activity.
In noninvasive neuroimaging, neural activity is inferred from local fluctuations in deoxyhemoglobin. A fundamental question of functional magnetic resonance imaging (fMRI) is whether the inferred neural activity is driven primarily by synaptic or spiking activity. ⋯ In colocalized recordings of neural and metabolic activity in cat primary visual cortex, we observed strong coupling between local field potentials (LFPs) and changes in tissue oxygen concentration in the absence of spikes. These results imply that the BOLD signal is more closely coupled to synaptic activity.
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The development of new treatments for depression is predicated upon identification of neural substrates and mechanisms that underlie its etiology and pathophysiology. The heterogeneity of depression indicates that its origin may lie in dysfunction of multiple brain regions. ⋯ We next revisit the functional differentiation of the hippocampus along the septo-temporal axis within the context of adult hippocampal neurogenesis and suggest that neurogenesis in the ventral dentate gyrus may be preferentially involved in regulation of emotion. Finally, we speculate on how increased adult hippocampal neurogenesis may modulate dentate gyrus function to confer the behavioral effects of antidepressants.
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Nature neuroscience · Jun 2007
Environmental enrichment in adulthood promotes amblyopia recovery through a reduction of intracortical inhibition.
Loss of visual acuity caused by abnormal visual experience during development (amblyopia) is an untreatable pathology in adults. We report that environmental enrichment in adult amblyopic rats restored normal visual acuity and ocular dominance. These effects were due to reduced GABAergic inhibition in the visual cortex, accompanied by increased expression of BDNF and reduced density of extracellular-matrix perineuronal nets, and were prevented by enhancement of inhibition through benzodiazepine cortical infusion.
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Nature neuroscience · Apr 2007
Pharmacotherapy for cognitive impairment in a mouse model of Down syndrome.
Ts65Dn mice, a model for Down syndrome, have excessive inhibition in the dentate gyrus, a condition that could compromise synaptic plasticity and mnemonic processing. We show that chronic systemic treatment of these mice with GABAA antagonists at non-epileptic doses causes a persistent post-drug recovery of cognition and long-term potentiation. These results suggest that over-inhibition contributes to intellectual disabilities associated with Down syndrome and that GABAA antagonists may be useful therapeutic agents for this disorder.
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Nature neuroscience · Apr 2007
ReviewChannel, neuronal and clinical function in sodium channelopathies: from genotype to phenotype.
What is the relationship between sodium channel function, neuronal function and clinical status in channelopathies of the nervous system? Given the central role of sodium channels in the generation of neuronal activity, channelopathies involving sodium channels might be expected to cause either enhanced sodium channel function and neuronal hyperexcitability associated with positive clinical manifestations such as seizures, or attenuated channel function and neuronal hypoexcitability associated with negative clinical manifestations such as paralysis. In this article, I review observations showing that changes in neuronal function and clinical status associated with channelopathies are not necessarily predictable solely from the altered physiological properties of the mutated channel itself. I discuss evidence showing that cell background acts as a filter that can strongly influence the effects of ion channel mutations.