Synaptic inputs

Epilepsy is a chronic neurological disorder characterized by recurrent seizures resulting from abnormal electrical activity in the brain. All experimental models for seizure generation are based on the administration of drugs (e.g. pilocarpine), on artificial increase in the concentrations of extracellular K+ (Ko) or on direct electric stimulation, to name a few. However, all these approaches may not accurately reflect the in vivo conditions, where otherwise normal neuronal activity can generate occasional seizures. It is thus important to better understand the pathological changes that may be

…Key questions remain on how synaptic connectivity relates to physiological properties and the anatomical detail needed to predict function. One modeling choi

Neurons receive distributed synaptic inputs over complex branched dendritic trees. These dendrites fundamentally allow for connectivity [1] and allow complex computations in space and time [2–4], but also impose metabolic costs in terms of maintenance and signal propagation [5]. Both the costs and benefits of dendritic trees are influenced by local diameters. The diameter profiles of dendrites are known to affect how much synaptic signals attenuate [6], how well mRNA or proteins can circulate [7], how quickly action potentials backpropagate [8], and even the strength of long-term synaptic plas

After excitotoxic lesions, subsets of striatal astrocytes undergo spontaneous neurogenic activation, leading to the local generation of a large number of neuroblasts for at least six months post-lesion. However, the functional integration of the lesion-induced neurons remains unclear. Fate mapping and 3D reconstruction analyses reveal that striatal neuroblasts undergo a maturation process in which they initially organize in clusters, subsequently disperse as individual cells, and gradually attain complex morphologies, often exhibiting dendritic spines. These neurons fail to express typical mar

As social creatures, we are impacted by the mere presence of our conspecifics. Behavioural adaptations, such as an increased drive for social interaction following isolation, have been linked to circuit changes involving oxytocin signalling, but the underlying molecular and cellular changes remain unclear. We used a juvenile social isolation paradigm, wherein male mice are single-housed between P21-P28, and their social behaviour is subsequently examined in a five-trial social recognition / interaction test. In this assay, we observed a lack of social habituation, whereas social recognition wa

Place Cells (PCs), are neurons that exhibit localized firing when an animal enters specific areas within an environment. Despite extensive experimental study revealing their link to cognitive functions, the precise cellular mechanisms underlying the transformation of a hippocampal neuron into a Place Cell remain incompletely understood. In our research, we employed a detailed computational model of a CA1 pyramidal neuron, considering both its morphology and biophysics. We aimed to elucidate how, and under what circumstances, such a neuron could encode a specific location based on the self-orga

Neurons rely on the interplay between dendritic morphology and ion channels to transform synaptic inputs into a sequence of somatic spikes. Detailed biophysical models with active dendrites have been instrumental for exploring this interaction. However, such models can be challenging to understand and validate due to the large number of parameters involved. In this work, we introduce DendroTweaks — a framework designed to illuminate how morpho-electric properties map to dendritic events, and how these dendritic events shape neuronal output. Through its graphical interface, users can access the

Altered neuronal excitability and synaptic inputs to motoneurons are part of the pathophysiology of Amyotrophic Lateral Sclerosis. The cAMP/PKA pathway regulates both of them but therapeutic interventions at this level are limited by the lack of knowledge about suitable pharmacological entry points. Here we used transcriptomics on microdissected and in situ motoneurons to reveal the modulation of PKA-coupled receptorome in SOD1(G93A) ALS mice, vs WT, demonstrating the dysregulation of multiple PKA-coupled GPCR, in particular on vulnerable MN, and the relative sparing of β-adrenergic. In vivo M

Aims: Investigation of differences in synaptic inputs from ventral tegmental area (VTA), ventral hippocampus (VH) and basolateral amygdala (BLA) on anterior cingulate cortex(ACC) neurons across all cortical layers between stress susceptible (SS) and stress resilient (SR) mice. Methods: Projections from VTA, VH and BLA excitatory neurons were labeled with cyan, green and yellow pre-eGRASP and ACC pyramidal neurons were labeled with post-eGRASP and TagRFP-T. Three weeks later, 10 mice were exposed to chronic social defeat stress for 10 days and on 11th day mice were divided into SS and SR groups

GABAergic inhibitory neurons fundamentally shape the activity and plasticity of cortical circuits. Subset of these neurons contains somatostatin (SOM); these cells play crucial roles in neuroplasticity, learning and memory in many brain areas including the hippocampus, and are implicated in neuropsychiatric diseases and neurodegenerative disorders. Two main types of SOM-containing cells in area CA1 of the hippocampus are oriens-lacunosum-moleculare (OLM) and hippocampo-septal cells. These cell types show many similarities in their soma-dendritic architecture, but they have different axonal tar

The primary function of the sensory cortex is to analyze incoming stimuli from the periphery, distinguishing and interpreting them to guide behavior. Among sensory stimuli, gustatory information enables animals to analyze the food identity and recognize the nutrition and hedonic values (e.g., palatable as sucrose, versus aversive as citric acid) to avoid poisons and regulate feeding behaviors, making it crucial for survival. Despite the importance of gustatory processing, our knowledge of the underlying neuronal circuits and their activity remains remarkably incomplete, especially compared to

The size and structure of the dendritic arbor play important roles in determining how synaptic inputs of neurons are converted to action potential output and how neurons are integrated in the surrounding neuronal network. Accordingly, neurons with aberrant morphology have been associated with neurological disorders. Dysmorphic, enlarged neurons are, for example, a hallmark of focal epileptogenic lesions like focal cortical dysplasia (FCDIIb) and gangliogliomas (GG). However, the regulatory mechanisms governing the development of dendrites are insufficiently understood. The evolutionary conserv

…can nonlinearly process distributed synaptic inputs. However, it is unclear how qualitative aspects of a dendritic tree, such as its branched morphology, its repetition of presynaptic inputs, voltage-gated ion channels, electrical properties and complex synapses, determine neural computation beyond this apparent nonlinearity. While it has been speculated that the dendritic tree of a neuron can be seen as a multi-layer neural network and it has been shown that such an architecture could be computationally strong,

…that receive and preprocess nearly all synaptic inputs in the brain. However, decades of experimental and theoretical research suggest that dendrites possess compelling computational capabilities that greatly influence neuronal and circuit functions. Notably, standard point-neuron networks cannot adequately capture most hallmark dendritic properties. Meanwhile, biophysically detailed neuron models are impractical for large-network simulations due to their complexity, and high computational co

Synaptic inputs onto single cortical neurons exhibit substantial diversity in their sensory-driven activity. What this diversity reflects is unclear, and appears counter-productive in generating selective somatic responses to specific stimuli. We propose that synaptic diversity supports computations that most effectively use information from upstream populations. To test this idea, we directly compare in silico synaptic weights for probabilistic decoder with in vivo synaptic input measurements. We define a decoder for a single sensory variable, orientation, that reads out the stimulus orientat

…increasing the gain of the respective synaptic inputs to higher-area neurons. As the synaptic inputs conveying competing stimuli converge and intermingle on postsynaptic neurons, impeding selective attentional addressing, presynaptic circuits might be the best target of top-down signals from higher areas of attentional control. If those signals enabled presynaptic circuits to selectively entrain postsynaptic neurons, this would be a mechanism for selective routing in accordance with the Communication-th

Many studies have investigated the major glutamatergic inputs to the cerebellum, mossy fibres and climbing fibres, however far less is known about its neuromodulatory inputs. In particular, anatomical studies have described cholinergic input to the cerebellum, yet little is known about its role(s). In this talk, I will present our recent findings which demonstrate that manipulating acetylcholine receptors in the cerebellum causes effects at both a cellular and behavioural level. Activating acetylcholine receptors alters the intrinsic properties and synaptic inputs of cerebellar output neurons,

Synaptic inputs on cortical dendrites are organized with remarkable subcellular precision at the micron level. This organization emerges during early postnatal development through patterned spontaneous activity and manifests both locally where synapses with similar functional properties are clustered, and globally along the axis from dendrite to soma. Recent experiments reveal species-specific differences in the local and global synaptic organization in mouse, ferret and macaque visual cortex. I will present a computational framework that implements functional and structural plasticity from sp

Spontaneous firing, observed in many neurons, is often attributed to ion channel or network level noise. Cortical cells during slow wave sleep exhibit transitions between so called Up and Down states. In this sleep state, with limited sensory stimuli, neurons fire in the Up state. Spontaneous firing is also observed in slices of cholinergic interneurons, cerebellar Purkinje cells and even brainstem inspiratory neurons. In such in vitro preparations, where the functional relevance is long lost, neurons continue to display a rich repertoire of firing properties. It is perplexing that these neuro