Synaptic connectivity

The Allen Institute has launched a new moonshot initiative on human brain health and disease called the Brain Health accelerator. This initiative aims to dramatically accelerate our understanding of human brain structure and function, identify the molecular, cellular and circuit basis of disease progression, and pioneer new therapeutic strategies targeting vulnerable and affected cell types. Our mission focuses on taking a human-centric approach to understanding and treating disease, combining a large-scale open science discovery approach across multiple diseases, AI-based disease modeling, an

…how this experience reorganizes the synaptic connectivity of neurons in the olfactory (piriform) cortex of the mouse. We developed an approach to measure synaptic connectivity in vivo, training a deep convolutional network to reliably identify monosynaptic connections from the spike-time cross-correlograms of 4.4 million single-unit pairs. This revealed that excitatory piriform neurons that respond similarly to each other are more likely to be connected. We asked whether thi

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

Synaptic and representational drift describe the dynamic changes in neuronal connections and activity over time. However, the relationship between these two processes remains elusive. Here, we integrated representational dynamics and synaptic drift into a firing rate model to explore the influence of synaptic drift on representational drift.In mouse auditory cortex, neuronal populations respond to stimuli in a clustered manner (Aschauer et al., 2022). Our model, comprising inhibitory and excitatory neurons, reproduces these response patterns, especially under inhibition-dominated conditions. W

Neuronal networks require precise coordination of excitatory and inhibitory synaptic connectivity to function properly. Regulation of parvalbumin-positive (PV+) interneuron activity is especially important for network function, and changes in PV+ interneuron activity correlate with an animal’s performance in learning tasks. Previously, changes in PV+ interneuron connectivity have been shown to regulate excitatory pyramidal cell activity. However, the mechanism via which PV+ interneurons control their own activity remains unknown. Here we used a chemogenetic approach to change the activity of P

…events in L2/3 neurons, which enhance synaptic plasticity and promote spiking. Such events greatly depend on the spatial and temporal arrangement of synaptic activity. However, the spatiotemporal relationship between HO

Instinctive behaviours, such as hunting and defense, are part of the natural repertoire of behaviours that are shaped by evolution and critical for the survival of both individual and species. The midbrain periaqueductal gray (PAG) has emerged as a bottleneck in the routing of most instinctive behaviours, translating sensory and cognitive information into an appropriate motor response. Yet, the exact mechanisms of this translation remain elusive. We aimed to identify the neural circuits in the brainstem bridging the initiation and execution of instinctive behaviours in mice by developing an an

The evolution and development of all organisms on earth relies on near-constant gravity. Experimental manipulations can create developmental conditions that have never been encountered during evolution, yet reveal developmental mechanisms based on informative phenotypic outcomes; classically, such experiments include transplantation of developing organs as well as pushing boundaries of environmental conditions.Here, we explore the outcome of Drosophila melanogaster brain development at hyper-gravity 10^2 to 10^3 times greater than conventional gravity on earth. Remarkably, Drosophila pupae ful

Ventral pathway circuits are constituted by the interconnected brain areas that are distributed throughout the brain. They are primarily involved in processing of object related information in brain. However, their role in object recognition memory (ORM) enhancement remains unknown. In this study, we show that an activation of each of the brain areas interconnected to ventral pathway circuits individually induced enhancement in ORM; however, same treatment in brain areas not interconnected to ventral pathway circuits produced no effect. Further study in perirhinal cortex (PRh), area V2 of visu

Memory is essential for behaviour, and it is supported in the brain by neuronal representations formed in the hippocampus and related structures. The gut microbiome can influence the brain and modify complex behaviours through interactions reported by the gut-brain-axis. Perturbations to the composition of the gut microbiome by environmental or genetic factors impact on mood and motivation and may affect memory. The strongest associations between gut microbiota, brain and memory originate from studies in germ-free mice, which are deprived of their microbiome from birth. The absence of microbes

Spiny projection neurons (SPNs) in the mouse striatum transform multimodal inputs from the cortex and thalamus into inhibitory outputs that regulate basal ganglia activity. SPNs are typically classified into major populations according to their output projection targets and their location within striatal anatomical and neurochemical domains. However, how the cellular and circuit diversity within these broad populations is established developmentally remains largely unknown. We have previously shown that SPNs derived from a distinct apical intermediate progenitor (aIP) pool are preferentially d

…structure whose role in regulating synaptic transmission in the healthy and diseased brain have not been extensively examined and may be relevant for understanding neuronal dysfunctions associated with myelin-related disorders. Here, we investigated excitatory (EPSCs) and inhibitory (IPSCs) post-synaptic currents in layer IV of the somatosensory (barrel) cortex using a cuprizone-induced demyelinati

Advancements in spatial imaging technologies (SIT) have broadened transcriptomic discovery capacity. Yet, development of orthogonal technologies for follow-up translational studies have trailed. We have developed MSIA that utilizes non-temporal, optical barcodes by combining the advantages of RNAscope™ double-Z probes and Hiplex v2 signal amplification technology.Fresh-frozen and FFPE brain coronal sections were collected from C57BL/6J mice of 3 age groups: 1 month, 6 months, and 12 months, respectively. MSIA was executed in 3 cycles, with 100 RNA targets in cycles 1&2 and then up to 4 pro

Memory engram cells, activated by learning, undergo input-specific augmentation in their synaptic connectivity (structure, strength and efficacy) to facilitate memory storage and recall. However, only a subset of these cells is reactivated upon retrieval, indicating potential differences in engram cell synaptic connectivity. In this study, we investigated structural synaptic connectivity differences between reactivated and non-reactivated hippocampal CA1 engram cells under conditions of neutral and aversive contextual memory valence. A combination of eGRASP (enhanced green fluorescent protein

…roles in excitability, maintaining synaptic connectivity, and even form specialised synapses capable of altering the transcriptional landscape of neurons.To further understand the role of cilia in postmitotic neurons, we generated human induced pluripotent stem cell lines (hiPSCs) with NPHP1-/- and

Brains of different individuals perform common essential functions despite differences in character, skills, perception or learning abilities. These fundamental observations suggest that neuronal computations exhibit different degrees of invariance to natural variability in the structure and dynamics of neuronal circuits. To understand the relation between structural and functional variability in a complex sensory network we focus on the olfactory bulb (OB) of larval zebrafish. The OB is optically accessible and sufficiently small to enable dense ultrastructural reconstructions of neuronal cir

…mechanosensory neurons and their postsynaptic circuits influence such diverse behaviors remains unclear. We previously identified nearly all mechanosensory neurons around the Drosophila head whose individual stimulation elicit aimed grooming of specific head parts (e.g. eyes or mouthparts) while their simultaneous stimulation elici

…comprehensive maps of their canonical synaptic architecture are missing. In mammals, three spatially separated main neuronal pathways through the BG were described - the direct, indirect, and hyperdirect pathways - that work together to orchestrate behavior. In songbirds, the cell types associated with these pathways appear intermingled in the basal ganglia nucleus Area X, essential for song learning. Here, we describe the first vertebrate basal ganglia connectome, compris

Understanding synaptic connectivity is crucial for understanding how neuronal networks contribute to specific brain functions. However, current methods can measure the functionality only of a limited number of synaptic connections in sufficient detail. Therefore, we evaluated the applicability of a voltage imaging method in acute rat hippocampal slices to map unitary synaptic connections between CA3 neurons by using Voltron, which can detect both action potentials and small subthreshold events, such as unitary EPSPs. These connections are crucial for major hippocampal memory functions; however

…This manifests as an augmentation of synaptic connectivity between these hippocampal subfields. Enhanced green fluorescent protein (GFP) reconstitution across synaptic partners (eGRASP) facilitates structural and electrophysiological analysis of input-specific synapses between engram cells. However, the protein landscape shaping and maintaining this enhanced engram synaptic connectivity remains unknown. Global proteomic analysis

…intracellular cytoskeleton, regulating synaptic connectivity and plasticity in response to extracellular cues. In particular, in the brain, β3 integrin interacts with the αV subunit to form the αVβ3 integrin heterodimer, which mediates adhesion strengthening of excitatory synapses in cortical pyramidal neurons.Alteration in integrin structure, expression or signalling is involved in the aetiology of various brain pathologies, including autism spectrum disorder (ASD) and epi

…methods for structural modulation of synaptic connections are still scarce. Here, we present a synthetic approach for synapse elimination via engineering of direct neuro-glial interactions which result in the uptake of synaptic components by astrocytes. The size-dependent synapse elimination in the CA3-CA1 circuit leads to a decline in synaptic connectivity, while the remaining synapses undergo reorganization o

…specific cells, guided by specific synaptic arrangements. Therefore, determining the architecture and properties of functioning microcircuits is fundamental to understand the brain’s action. However, our current knowledge of human microcircuits is extremely limited, and relies heavily on assumptions from rodent research. Using tissue resected from 13 temporal lobe epilepsy patients, we perform multicellular patch-clamp based microcircuit analysis (n=80 recordings) to characterize synaptic connectivity in the human hippocampa

…measured neural activities and synaptic strengths. However, the scope of these networks remained limited as their connectivity needed to be designed by hand or fitted by complex machine learning algorithms to yield stable activity and computations. Here we present a method to effic