Induced chromosome deletions cause hypersociability and other features of Williams-Beuren syndrome in mice.

The neurodevelopmental disorder Williams-Beuren syndrome is caused by spontaneous approximately 1.5 Mb deletions comprising 25 genes on human chromosome 7q11.23.

Integration of light-controlled neuronal firing and fast circuit imaging.

For understanding normal and pathological circuit function, capitalizing on the full potential of recent advances in fast optical neural circuit control will depend crucially on fast, intact-circuit readout technology. First, millisecond-scale optical control will be best leveraged with simultaneous millisecond-scale optical imaging. Second, both fast circuit control and imaging should be adaptable to intact-circuit preparations from normal and diseased subjects.

High-speed imaging reveals neurophysiological links to behavior in an animal model of depression.

The hippocampus is one of several brain areas thought to play a central role in affective behaviors, but the underlying local network dynamics are not understood. We used quantitative voltage-sensitive dye imaging to probe hippocampal dynamics with millisecond resolution in brain slices after bidirectional modulation of affective state in rat models of depression. We found that a simple measure of real-time activity-stimulus-evoked percolation of activity through the dentate gyrus relative to the hippocampal output subfield-accounted for induced changes in animal behavior independent of the underlying mechanism of action of the treatments.

A study of the involvement of melanin-concentrating hormone receptor 1 (MCHR1) in murine models of depression.

Background: Most antidepressant medications target central monoamine systems and are often characterized by limited efficacies and unwanted side effects. Thus, significant efforts are ongoing to identify novel targets for the treatment of depression. Growing evidence suggests that neuropeptides play a role in the pathophysiology of depression.

Genetic inactivation of melanin-concentrating hormone receptor subtype 1 (MCHR1) in mice exerts anxiolytic-like behavioral effects.

The biological effects of the melanin-concentrating hormone (MCH) are mediated by the melanin concentrating hormone receptor 1 (MCHR1) in mice. This receptor is enriched in brain areas that are involved in the modulation of mood and affect, suggesting that MCH-dependent signaling may influence neurobiological mechanisms underlying fear and anxiety processes. To test this, we have generated mice lacking functional MCHR1 and characterized phenotypic traits using a number of behavioral tests.

The neuroprotective effects of virally-derived caspase inhibitors p35 and crmA following a necrotic insult.

Neuronal excitotoxicity causes energetic impairment and the ensuing cell death has historically been regarded as necrotic. Recent findings, however, indicate that apoptosis may participate in excitotoxicity. Here we examined the neuroprotective mechanisms of the well-characterized viral caspase inhibitors, p35 and crmA, following domoic acid-induced excitotoxicity in hippocampal neurons.

The exacerbation of hippocampal excitotoxicity by glucocorticoids is not mediated by apoptosis.

Both endogenous and exogenous glucocorticoids (GCs) are known to cause apoptosis in a number of peripheral tissues and in some cases in the CNS. Additionally, GCs can exacerbate the neuron loss associated with such acute neurological insults as hypoxia-ischemia, excitotoxicity, and metabolic disruption. This exacerbation is accompanied by increased accumulation of glutamate in the synapse, excessive cytosolic calcium, and increased oxygen radical activity, markers usually attributed to pathways of necrotic cell death.