Topic: excitatory neurons

Classical views suggest that memories are stored in assemblies of excitatory neurons that become strongly interconnected during learning. However, recent experimental and theoretical results have challenged this view, leading to the hypothesis that memories are encoded in assemblies containing both excitatory (E) and inhibitory (I) neurons. Understanding the effects of these E-I assemblies on memory function is therefore essential. Using a biologically constrained model of an olfactory memory network, I will first describe how introducing E-I assemblies reorganizes odor-evoked activity pattern

Focal neocortical epilepsy is associated with intermittent brief population discharges (interictal spikes), which resemble sentinel spikes that often occur at the onset of seizures. Why interictal spikes self-terminate whilst seizures persist and propagate is incompletely understood, but is likely to relate to the intermittent collapse of feed-forward GABAergic inhibition. Inhibition could fail through multiple mechanisms, including (i) an attenuation or even reversal of the driving force for chloride in postsynaptic neurons because of intense activation of GABAA receptors, (ii) an elevation o

In this study, we aim to broaden our understanding of the mouse’s primary visual cortex by modeling data provided by the datasets from Stringer et al. (2019) and the Allen Institute. We investigated the roles of the different excitatory and inhibitory cell types in the visual cortex whose functions remain unclear. Using the Stringer dataset, we explored the correlation between the activity of excitatory cells in the mouse visual cortex and mouse running behavior without any visual input. Principle Component Analysis (PCA) was applied to reduce the dimension of our neuron activity data of 119

Evolutionarily, the expansion of the human neocortex accounts for many of the unique cognitive abilities of humans. This expansion appears to reflect the increased proliferative potential of basal progenitors (BPs) in mammalian evolution. Further cortical progenitors generate both glutamatergic excitatory neurons (ENs) and GABAergic inhibitory interneurons (INs) in human cortex, whereas they produce exclusively ENs in rodents. The increased proliferative capacity and neuronal subtype generation of cortical progenitors in mammalian evolution may have evolved through epigenetic alterations. Howe

The ability to discriminate different sensory patterns by disentangling their neural representations is an important property of neural networks. While a variety of learning rules are known to be highly effective at fine-tuning synapses to achieve this, less is known about how different cell types in the brain can facilitate this process by providing architectural priors that bias the network towards sparse, selective, and discriminable representations. We studied this by simulating a neuronal network modelled on the dentate gyrus—an area characterised by sparse activity associated with patter

Learning is known to induce the formation of new dendritic spines, but despite decades of effort, the functional properties of new spines in vivo remain unknown. Here, using a combination of longitudinal in vivo 2-photon imaging of the glutamate reporter, iGluSnFR, and correlated electron microscopy (CLEM) of dendritic spines on the apical dendrites of L2/3 excitatory neurons in the motor cortex during motor learning, we describe a framework of new spines' formation, survival, and resulting function. Specifically, our data indicate that the potentiation of a subset of clustered, pre-existing s

Optogenetics is a powerful tool that allows experimentalists to perturb neural circuits. What can we learn about a network from observing its response to perturbations? I will first describe the results of optogenetic activation of inhibitory neurons in mice cortex, and show that the results are consistent with inhibition stabilization. I will then move to experiments in which excitatory neurons are activated optogenetically, with or without visual inputs, in mice and monkeys. In some conditions, these experiments show a surprising result that the distribution of firing rates is not significan

Temporal lobe epilepsy (TLE) is a progressive disorder mediated by pathological changes in molecular cascades and neural circuit remodeling in the hippocampus resulting in increased susceptibility to spontaneous seizures and cognitive dysfunction. Targeting these cascades could prevent or reverse symptom progression and has the potential to provide viable disease-modifying treatments that could reduce the portion of TLE patients (>30%) not responsive to current medical therapies. Changes in GABA(A) receptor subunit expression have been implicated in the pathogenesis of TLE, and the Janus Kinas

Animals depend on fast and reliable detection of novel stimuli in their environment. Neurons in multiple sensory areas respond more strongly to novel in comparison to familiar stimuli. Yet, it remains unclear which circuit, cellular, and synaptic mechanisms underlie those responses. Here, we show that spike-timing-dependent plasticity of inhibitory-to-excitatory synapses generates novelty responses in a recurrent spiking network model. Inhibitory plasticity increases the inhibition onto excitatory neurons tuned to familiar stimuli, while inhibition for novel stimuli remains low, leading to a n

The Kappa Opioid Receptor as Potential Drug Target in TLE Over the last decades, neuropeptides and their receptors received increasing interest as drug targets for multiple purposes. Our interest focuses on the endogenous opioid system and more specifically on dynorphins and the kappa opioid receptor (KOR). Activation of KOR blocks presynaptic Calcium channels and facilitates postsynaptic Potassium release, thereby dampening signal transduction. As KORs are situated on excitatory neurons in the hippocampus, this makes them an interesting target in temporal lobe epilepsy.

The brain continuously encodes new information as memories. At the synaptic level, memory formation is enabled by adjusting connections between activated excitatory neurons in the cortex, with mirroring inhibitory activity ensuring stable storage. Particularly, synaptic plasticity occurs as memory reactivation takes place during sleep, contributing to increased memory stability. However, the mechanism by which reactivation mediates plasticity to balance network currents for stable memory storage remains unclear. Here, we investigated whether a newly proposed form of codependent plasticity coul

Network models of cortex typically focus on excitatory population dynamics, relegating inhibition to a support role. However, recent studies have shown that memories can be encoded by both excitatory and inhibitory neurons (EI engrams), adding to the evidence of the functional importance of inhibitory neurons beyond mere stabilization. The functional consequence of such EI engrams is unclear, and the synaptic plasticity rules that could sustain them are unknown. Here, we explore in silico a mechanism for EI engrams storage and recall to glean possible computational benefits of such engrams ove