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Pathogenesis for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) remains largely unknown. Using a mouse model of ALS and FTD, the authors found that somatostatin interneurons in motor cortex were hyperactive. This hyperactivity led to the disinhibition of pyramidal neurons and correlated with signs of excitotoxicity. Ablating somatostatin interneurons restored the excitability of pyramidal cells to a normal level and prevented neurodegeneration.
Subsets of hippocampal neurons store map-like representations of experienced environments. The authors optogenetically silenced a neuronal population active in an environment and saw an alternative map emerge. In a cocaine-paired environment, this approach neutralized drug-place preference, implicating recoding of spatial memory engrams as strategy for alleviating maladaptive behaviors.
Dopaminergic neurons in the ventral tegmental area (VTA) contribute to mediating stress susceptibility and resilience. The authors demonstrate that noradrenergic neurons in the locus coeruleus can drive the activity of these dopaminergic VTA neurons to generate a resilient response to chronic stress.
Increases in synaptic inhibition have been proposed to underlie divisive normalization in distal neural networks. Here, using optogenetic stimulation and intracellular recordings in mouse visual cortex, the authors argue that normalization is a result of a decrease in synaptic excitation.
