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Shepherd, G. M.

Publications and source records attributed to Shepherd, G. M..

3 recordsLinked to original sources

NetPyNE: a tool for data-driven multiscale modeling of brain circuits

Biophysical modeling of neuronal networks helps to integrate and interpret rapidly growing and disparate experimental datasets at multiple scales. The NetPyNE tool (www.netpyne.org) provides both programmatic and graphical interfaces to develop data-driven multiscale network models in NEURON. NetPyNE clearly separates model parameters from implementation code. Users provide specifications at a high level via a standardized declarative language, e.g., a connectivity rule, instead of tens of loops to create millions of cell-to-cell connections. Users can then generate the NEURON network, run efficiently parallelized simulations, optimize and explore network parameters through automated batch runs, and use built-in functions for visualization and analysis - connectivity matrices, voltage traces, raster plots, local field potentials, and information theoretic measures. NetPyNE also facilitates model sharing by exporting and importing using NeuroML and SONATA standardized formats. NetPyNE is already being used to teach computational neuroscience students and by modelers to investigate different brain regions and phenomena.

neuroscience↗

Long-range inhibitory intersection of a retrosplenial thalamocortical circuit by apical tuft-targeting CA1 neurons

Dorsal hippocampus, retrosplenial cortex (RSC), and anterior thalamic nuclei (ATN) interact to mediate diverse cognitive functions, but the cellular basis for these interactions is unclear. We hypothesized a long-range circuit converging in layer 1 (L1) of RSC, based on the pathway anatomy of GABAergic CA1 retrosplenial-projecting (CA1-RP) neurons and thalamo-restrosplenial projections from ATN. We find that CA1[->]RSC projections stem from GABAergic neurons with a distinct morphology, electrophysiology, and molecular profile, likely corresponding to recently described Ntng1-expressing hippocampal interneurons. CA1-RP neurons monosynaptically inhibit L5 pyramidal neurons, principal outputs of RSC, via potent GABAergic synapses onto apical tuft dendrites in L1. These inhibitory inputs align precisely with L1-targeting thalamocortical excitatory inputs from ATN, particularly the anteroventral nucleus, forming a convergent circuit whereby CA1 inhibition can intercept ATN excitation to co-regulate RSC activity. Excitatory axons from subiculum, in contrast, innervate proximal dendrites in deeper layers. Short-term synaptic plasticity differs at each connection. Chemogenetically abrogating inhibitory CA1[->]RSC or excitatory ATN[->]RSC connections oppositely affects the encoding of contextual fear memory. Collectively, our findings identify multiple cellular mechanisms underlying hippocampo-thalamo-retrosplenial interactions, establishing CA1 RSC-projecting neurons as a distinct class with long-range axons that target apical tuft dendrites, and delineating an unusual cortical circuit in the RSC specialized for integrating long-range inhibition and thalamocortical excitation.

neuroscience↗

Long-range inputs and H-current regulate different modes of operation in a multiscale model of mouse M1 microcircuits

We developed a biophysically detailed multiscale model of mouse primary motor cortex (M1) with over 10,000 neurons and 35 million synapses. We focused on intratelencephalic (IT) and pyramidal-tract (PT) neurons of layer 5 (L5), which were modeled at high multicompartment resolution. Wiring densities were based on prior detailed measures from mouse slice, and depended on cell class and cortical depth at sublaminar resolution. Prominent phase-amplitude-coupled delta and gamma activity emerged from the network. Spectral Granger causality analysis revealed the dynamics of information flow through populations at different frequencies. Stimulation of motor vs sensory long-range inputs to M1 demonstrated distinct intra- and inter-laminar dynamics and PT output. Manipulating PT Ih altered PT activity, supporting the hypothesis that Ih neuromodulation is involved in translating motor planning into execution. Our model sheds light on the multiscale dynamics of cell-type-specific M1 circuits and how connectivity relates to dynamics.

neuroscience↗