Synaptic connections

Over the past decade our community has made substantial progress in the construction of anatomically detailed network models of the cortical tissue. Thanks to advances in computer hardware and simulation technology, researchers can now routinely work with these models at the natural density of neurons and synapses. Moreover, the availability of cloud services means that such investigations can be carried out without having to install either the model or the simulation software. A recent workshop analyzed the impact of a specific model of the cortical microcircuit, published ten years ago . The

We present, for the first time, insights into functional synchronization of individual neurons under a complete anatomical neural connectivity map at a massive scale. While functional synchrony has been extensively studied as a mechanism of information processing in the brain, previous work has been limited to small populations of neurons in vitro, analyses across entire brain regions, or simulations in silico. Here, we leverage the large scale connectomics dataset MICrONS to analyze synchrony through the proxy of Pearson correlation across neurons at a larger scale in vivo with direct anatomi

…which can be attained via direct synaptic connections. Phylogenetically, the main purpose of the brain is the active interaction with the environment which suggests the presence of an alternative neural coordination mechanism, namely one that is mediated by a feedback loop involving the outside world. In this context we study the coordination of otherwise isolated neural clusters via 'force coupling', viz exclusively through the reactive forces of the body. Coordination arises when a given neural net reacts to the

The calretinin-positive (CR+) neurons of the paraventricular thalamic nucleus (PVT) have been recognized to play pivotal role in modulating stress and arousal states. In the accompanying poster (Kota et al.), we defined several brain regions containing glutamatergic, GABAergic or mixed populations of neurons that project to PVT. In this study, we mapped cortical and subcortical afferents in the PVT and examined their distribution relative to the PVT/CR+ neuron population. We used vGLUT2-Cre, vGAT-Cre, and vGLUT2-Cre/vGAT-Flp double transgenic mouse strains to explore subcortical inputs via ant

Establishing, maintaining and dynamically modifying synaptic connections is a key principle of neuronal computations. The underlying molecular resource of these processes is synaptic proteins. Tight control of protein levels across neurons is crucial to ensure synaptic function. Changes in the synaptic proteome have been associated with compromised synaptic function and in severe cases various diseases. Among the major factors in regulating protein levels are thought to be protein synthesis, trafficking and degradation. While there is substantial literature on protein synthesis, both trafficki

Stable neural ensembles are often thought to underlie stable learned behaviors and memory. Recent longitudinal experiments, however, that tracked the activity of the same neurons over days to weeks have shown that neuronal activity patterns can change over extended timescales even if behaviors remain the same – a phenomenon termed representational drift. Here we test whether neural circuit remodeling (defined as any change in structural connectivity) contributes to representational drift. To do this, we tracked how hippocampal CA1 spatial representations of a familiar environment change with t

…governed by the intricate interplay of synaptic connections within neural populations. Extensive theoretical and empirical investigations have underscored the influential role of synaptic weights in shaping both the collective dynamics and the fluctuations of neural activity. A salient inquiry arising from this understanding pertains to the mech

How changes in synaptic connections underlie learning and memory is a central question in Neuroscience. Previous modeling efforts focused on biologically realistic learning rules and dynamics, but these rules usually produce bimodal weight distributions that are not aligned with experimentally observed lognormal distributions of synaptic weights. How biological learning rules preserve such unimodal distributions and at the same time retain information, i.e., learn, remains unknown. Here, we take a game-theoretical approach, asking whether learning is possible under the constraint of retaining

There is strong evidence that alterations in the structural and functional properties of synaptic connections during learning are underlying the formation of long-term memories. However, what specific changes in the architecture of the neuronal network are mediated by learning-induced plasticity is still poorly understood. A major limiting factor of current in vivo imaging studies of synaptic dynamics is that typically only at a small number of synapses are assessed in a given animal, typically tens to hundreds. Here, we started to apply longitudinal in vivo two-photon imaging of more than a m

…circuits by influencing the number of synaptic connections, both excitatory and inhibitory. This study investigates the microglial involvement in DS-related connectivity deficits. Using in vivo mesoscale wide-field calcium imaging, we analyzed the cortical connectivity of Ts65Dn and euploid mice injected retroorbitally with a CAMKII-GCaMP7f viral vector, in response to a drug effective in blocking neuron

Multisensory integration is a sensory processing mechanism that integrate input information from different sensory modalities, occurring during sensory reception and perception. However, the underlying neuronal circuit to integrate sensory information is still unknown. We featured anterolateral visual area (AL), which has axonal projection from primary sensory cortexes, and try to clarify the mechanism underpinning sensory information processing and integration in AL. We first visualized neuronal response to sensory input (whisker stimulation and auditory representation) in AL by in vivo Ca2+

Establishing synaptic connections between neurons is essential for neuronal circuitry and efficient brain communication While the role of neuronal activity in refining and maintaining synapses is well known, we focus on its role, specifically spontaneous neurotransmitter release, for synapse formation between dentate gyrus axons, the mossy fibres (MF), onto CA3 pyramidal cells in the hippocampus. Neurotransmitter release occurs through two primary modes: action potential induced release and spontaneous fusion of synaptic vesicles. These modes are underpinned by distinct pools of vesicles, exhi

…of projections is akin to changing synaptic connections in the neural circuit

…that make an excessive number of synaptic connections. Later, a wave of neuronal remodeling radically reshapes nervous system wiring and cell numbers through the selective elimination of excess synapses, axons and dendrites, and even whole neurons. This remodeling is widespread across the nervous system, extensive in terms of how much individual brain regions can change (e.g. in some cases 50% of neurons integrated into a brain circuit are eliminated), and thought to be essential for optimizing nervous system fu

…in deep sensory networks with plastic synaptic connections. Experience-dependent plasticity presumably exploits temporal contingencies between sensory inputs to build these internal representations. However, the precise mechanisms underlying plasticity remain elusive. We derive a local synaptic plasticity model inspired by self-supervised machine learning techniques that shares a deep conceptual connection to Bienenstock-Coo

Microglia, traditionally classified as immune-responsive, adjust synaptic connections during development and disease. However, their role in the adult nervous system has been mostly diminished to an observer. In my research group, we are interested in how microglia are involved in establishing and maintaining accurate neuronal circuit function in the retina and in the visual cortex. In my talk, I will introduce our strategies how to decipher the microglia’s functional identity and how this information guided us to microglia enabled extracellular matrix remodeling and reinstatment of juvenile-l

Gradient descent is a central tool in modern machine learning, largely because it scales well to train large networks on computationally challenging tasks. As such, computational neuroscientists are exploring potential means by which the brain could leverage gradient descent. However, it is unlikely that the brain could implement perfect gradient descent, but instead could rely on using approximations of the true gradient signal. Therefore, it is likely that the gradient estimates used by the brain would have both bias and variance. Here, we use model agnostic mathematical analysis and simulat

…called microglia, in sculpting of synaptic connections during development and their relevance to autism, schizophrenia and other brain disorders. Her recent work revealed a key role for microglia and a group of immune related molecules called complement in normal developmental synaptic pruning, a normal process required to establish precise brain wiring. Emerging evidence suggests aberrant regulation of this pruning pathway may contribute to synaptic and cognitive dysfunction in a host of brain disorders,

…and store that information amongst the synaptic connections between the neurons that both comprise the network and govern its function. The strength and organization of synaptic connections adjust during learning, but many cognitive neural systems are multifunctional, making it unclear how continuous activity alternates between the transient and discrete cognitive functions like encoding current information and recollecting past information, without changing the connections amongst the

…and store that information amongst the synaptic connections between the neurons that both comprise the network and govern its function. The strength and organization of synaptic connections adjust during learning, but many cognitive neural systems are multifunctional, making it unclear how continuous activity alternates between the transient and discrete cognitive functions like encoding current information and recollecting past information, without changing the connections amongst the

…neural responses and the stability of synaptic connections that form memory engrams. However, recent experimental findings have challenged this idea, revealing that neural population activity in circuits involved in sensory perception, motor planning and spatial memory continually change over time during familiar behavioural tasks. This continual cha

The establishment of synaptic connections is essential for normal brain function, yet the molecular mechanisms responsible for the precise connectivity of specific neural circuits remain largely unknown. Previous work has shown that the assembly of cortical circuits requires specific functions of molecular signalling complexes at different classes of synapses. In this talk, I will describe the molecular logic through which specific pyramidal cell-interneuron circuits are established in the cerebral cortex of the mouse, and how alterations in some of these connectivity motifs might be liked to

…populations and much more structured synaptic connections. Unlike typical simplified cortical network models, real network

The concept of a dynamic excitation / inhibition ratio, that can shape information flow in cortical circuits during complex behavioural tasks due to circuit disinhibition, has recently arisen as an important and conserved processing motif. It has been also recognized that, in cortical circuits, a subpopulation of GABAergic cells that express vasoactive intestinal polypeptide (VIP) innervates selectively inhibitory interneurons, providing for circuit disinhibition as a possible outcome, depending on the network state and behavioural context. In this talk, I will highlight the latest discoveries