Topic: synaptic inhibition

Schizophrenia is a complex disorder known for its positive symptoms: delusions and hallucinations. However, the impact of schizophrenia on function is mostly due to its executive dysfunction. Mechanistically, it is known that the prefrontal cortex (PFC) is dysfunctional in this disorder and that there is a general excitatory/inhibitory (E/I) imbalance in the schizophrenia brain. However, whether schizophrenia executive dysfunction can be specifically attributed to prefrontal E/I imbalance is unknown. Here, through a series of experiments across schizophrenia-relevant mouse models, we show the

In mouse models of Down syndrome (DS), cognitive deficits such as memory impairment are believed to be caused by overinhibition. However, recent studies indicate that the overexpression of Grik1, a gene mainly expressed at interneurons in the hippocampus, could be a key driver of memory deficits in individuals with DS due to a bidirectional alteration of synaptic inhibition on CA1 pyramidal cells (Valbuena et al, Nature Comms. 2019, 10:4991). Remarkably, normalizing Grik1 dosage in the Ts2Cje mouse model of DS specifically restores spatial memory and reverses the bidirectional alterations to C

Identifying and avoiding potentially harmful food is crucial for the survival of many organisms. Conditioned taste aversion (CTA) is an associative learning paradigm when a novel appetitive tastant (e.g., saccharin) paired with a malaise-inducing agent, such as intraperitoneal injection of lithium chloride (LiCl), induces an aversion towards the same tastant when presented again. Recently, we have demonstrated that taste valence is encoded, at least in part, by changes in the intrinsic and synaptic properties of layer V/VI projecting neurons in aIC. Recent rodent studies have demonstrated that

The primary olfactory cortex (piriform cortex) is a well-established epileptogenic site with the potential to amplify and generalize seizures. Disinhibition, caused by the synaptic inhibition of inhibitory neurons by other inhibitory neurons, increases the excitability of principal neurons and has been proposed as a contributing factor in numerous neurological diseases, including epilepsy. Therefore, unravelling inhibitory microcircuits in the piriform cortex may uncover new therapeutic avenues for treating epilepsy. Our study used whole-cell recordings from identified classes of inhibitory in

Optimal mammalian brain function relies on well-organized neuronal networks. GABAergic inhibitory interneurons precisely target subcellular regions to modulate synaptic inhibition and influence the timing of different neural networks. However, the molecular mechanisms guiding the assembly and stability of inhibitory synapses remain largely undefined. In this study, we explored an extracellular signalling pathway that uphold synaptic inhibition at a central inhibitory synapse. Using the cerebellar basket cell to Purkinje cell connection as a model, we discovered an unconventional paracrine path