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Role of interneuron subtypes in controlling trial-by-trial output variability in the neocortex.

ABSTRACT: Trial-by-trial variability is a ubiquitous property of neuronal activity in vivo which shapes the stimulus response. Computational models have revealed how local network structure and feedforward inputs shape the trial-by-trial variability. However, the role of input statistics and different interneuron subtypes in this process is less understood. To address this, we investigate the dynamics of stimulus response in a cortical microcircuit model with one excitatory and three inhibitory interneuron populations (PV, SST, VIP). Our findings demonstrate that the balance of inputs to different neuron populations and input covariances are the primary determinants of output trial-by-trial variability. The effect of input covariances is contingent on the input balances. In general, the network exhibits smaller output trial-by-trial variability in a PV-dominated regime than in an SST-dominated regime. Importantly, our work reveals mechanisms by which output trial-by-trial variability can be controlled in a context, state, and task-dependent manner.

SUBMITTER: Guo L

PROVIDER: S-EPMC10449833 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Role of interneuron subtypes in controlling trial-by-trial output variability in the neocortex.

Guo Lihao L Kumar Arvind A

Communications biology 20230825 1

Trial-by-trial variability is a ubiquitous property of neuronal activity in vivo which shapes the stimulus response. Computational models have revealed how local network structure and feedforward inputs shape the trial-by-trial variability. However, the role of input statistics and different interneuron subtypes in this process is less understood. To address this, we investigate the dynamics of stimulus response in a cortical microcircuit model with one excitatory and three inhibitory interneuro ...[more]

PMID: 37620550

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Project description:The activity of excitatory neurons is controlled by a highly diverse population of inhibitory interneurons. These cells show a high level of physiological, morphological and neurochemical heterogeneity, and play highly specific roles in neuronal circuits. In the mammalian hippocampus, these are divided into 21 different subtypes of GABAergic interneurons based on their expression of different markers, morphology and their electrophysiological properties. Ideally, all can be marked using an antibody directed against the inhibitory neurotransmitter GABA, but parvalbumin, calbindin, somatostatin, and calretinin are also commonly used as markers to narrow down the specific interneuron subtype. Here, we describe a journey to find the necessary immunological reagents for studying GABAergic interneurons of the mouse hippocampus. Based on web searches there are several hundreds of different antibodies on the market directed against these four markers. Searches in the literature databases allowed us to narrow it down to a subset of antibodies most commonly used in publications. However, in our hands the most cited ones did not work for immunofluorescence stainings of formaldehyde fixed tissue sections and cultured hippocampal neurons, and we had to immunostain our way through thirteen different commercial antibodies before finally finding a suitable antibody for each of the four markers. The antibodies were evaluated based on signal-to-noise ratios as well as if positive cells were found in layers of the hippocampus where they have previously been described. Additionally, the antibodies were also tested on sections from mouse spinal cord with similar criteria for specificity of the antibodies. Using the antibodies with a high rating on pAbmAbs, an antibody review database, stainings with high signal-to-noise ratios and location of the immunostained cells in accordance with the literature could be obtained, making these antibodies suitable choices for studying the GABAergic system.

Dataset Information

Role of interneuron subtypes in controlling trial-by-trial output variability in the neocortex.

Publications

Role of interneuron subtypes in controlling trial-by-trial output variability in the neocortex.

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