Biology subjects

Hage, T. A.

Publications and source records attributed to Hage, T. A..

4 recordsLinked to original sources

bioRxiv2021

Connectivity and Synaptic Physiology in the Mouse and Human Cortex

To elucidate cortical microcircuit structure and synaptic properties we present a unique, extensive, and public synaptic physiology dataset and analysis platform. Through its application, we reveal principles that relate cell type to synapse properties and intralaminar circuit organization in the mouse and human cortex. The dynamics of excitatory synapses align with the postsynaptic cell subclass, whereas inhibitory synapse dynamics partly align with presynaptic cell subclass but with considerable overlap. Despite these associations, synaptic properties are heterogeneous in most subclass to subclass connections. The two main axes of heterogeneity are strength and variability. Cell subclasses divide along the variability axis, while the strength axis accounts for significant heterogeneity within the subclass. In human cortex, excitatory to excitatory synapse dynamics are distinct from those in mouse and short-term plasticity varies with depth across layers 2 and 3. With a novel connectivity analysis that enables fair comparisons between circuit elements, we find that intralaminar connection probability among cell subclasses exhibits a strong layer dependence.These and other findings combined with the analysis platform create new opportunities for the neuroscience community to advance our understanding of cortical microcircuits.

neuroscience↗

bioRxiv2019

Distribution and strength of interlaminar synaptic connectivity in mouse primary visual cortex revealed by two-photon optogenetic stimulation

The most common synaptic connections between neurons in different cortical layers form the basis of the canonical cortical microcircuit. Understanding of cortical function will require further development and application of methods to efficiently characterize synaptic connections within and outside of the canonical pathway. Accordingly, we measured synaptic inputs onto superficial excitatory neurons in response to sequential two-photon optogenetic stimulation of neurons in deeper layers. Layer 4 excitatory neurons and somatostatin-neurons within layer 2/3 represented the most common sources of input. Although connections from excitatory and somatostatin-neurons in layer 5 were less common, the amplitudes of synaptic responses were equally strong. We examined synaptic strength across all connections, as well as the relationships between the strength of connections diverging from a common presynaptic neuron or converging to a single target. While the overall distribution indicates synaptic weight is concentrated to a few connections, strong excitatory connections are distributed across cells.

neuroscience↗

bioRxiv2018

Sparse recurrent excitatory connectivity in the cortical microcircuit of the adult mouse and human

Generating a comprehensive description of cortical networks requires a large-scale, systematic approach. To that end, the Allen Institute is engaged in a pipeline project using multipatch electrophysiology, supplemented with 2-photon optogenetics, to characterize connectivity and synaptic signaling between classes of neurons in adult mouse and human cortex. We focus on producing results detailed enough for the generation of computational models and enabling comparison with future studies. Here we report our examination of intralaminar connectivity within each of several classes of excitatory neurons. We find that connections are sparse but present among all excitatory cell types and layers we sampled, with the most sparse connections in layers 5 and 6. Almost all mouse synapses exhibited short-term depression with similar dynamics. Synaptic signaling between a subset of layer 2/3 neurons; however, exhibited facilitation. These results contribute to a body of evidence describing recurrent excitatory connectivity as a conserved feature of cortical microcircuits.

neuroscience↗

bioRxiv2017

A suite of transgenic driver and reporter mouse lines with enhanced brain cell type targeting and functionality

Modern genetic approaches are powerful in providing access to diverse types of neurons within the mammalian brain and greatly facilitating the study of their function. We here report a large set of driver and reporter transgenic mouse lines, including 23 new driver lines targeting a variety of cortical and subcortical cell populations and 26 new reporter lines expressing an array of molecular tools. In particular, we describe the TIGRE2.0 transgenic platform and introduce Cre-dependent reporter lines that enable optical physiology, optogenetics, and sparse labeling of genetically-defined cell populations. TIGRE2.0 reporters broke the barrier in transgene expression level of single-copy targeted-insertion transgenesis in a wide range of neuronal types, along with additional advantage of a simplified breeding strategy compared to our first-generation TIGRE lines. These novel transgenic lines greatly expand the repertoire of high-precision genetic tools available to effectively identify, monitor, and manipulate distinct cell types in the mouse brain.

neuroscience↗