Dataset Information

The Impact of Structural Heterogeneity on Excitation-Inhibition Balance in Cortical Networks.

ABSTRACT: Models of cortical dynamics often assume a homogeneous connectivity structure. However, we show that heterogeneous input connectivity can prevent the dynamic balance between excitation and inhibition, a hallmark of cortical dynamics, and yield unrealistically sparse and temporally regular firing. Anatomically based estimates of the connectivity of layer 4 (L4) rat barrel cortex and numerical simulations of this circuit indicate that the local network possesses substantial heterogeneity in input connectivity, sufficient to disrupt excitation-inhibition balance. We show that homeostatic plasticity in inhibitory synapses can align the functional connectivity to compensate for structural heterogeneity. Alternatively, spike-frequency adaptation can give rise to a novel state in which local firing rates adjust dynamically so that adaptation currents and synaptic inputs are balanced. This theory is supported by simulations of L4 barrel cortex during spontaneous and stimulus-evoked conditions. Our study shows how synaptic and cellular mechanisms yield fluctuation-driven dynamics despite structural heterogeneity in cortical circuits.

SUBMITTER: Landau ID

PROVIDER: S-EPMC5158120 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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The Impact of Structural Heterogeneity on Excitation-Inhibition Balance in Cortical Networks.

Landau Itamar D ID Egger Robert R Dercksen Vincent J VJ Oberlaender Marcel M Sompolinsky Haim H

Neuron 20161117 5

Models of cortical dynamics often assume a homogeneous connectivity structure. However, we show that heterogeneous input connectivity can prevent the dynamic balance between excitation and inhibition, a hallmark of cortical dynamics, and yield unrealistically sparse and temporally regular firing. Anatomically based estimates of the connectivity of layer 4 (L4) rat barrel cortex and numerical simulations of this circuit indicate that the local network possesses substantial heterogeneity in input ...[more]

PMID: 27866797

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Project description:The medial prefrontal cortex (mPFC) controls behavior via connections with limbic excitatory afferents that engage various inhibitory motifs to shape mPFC circuit function. The dynorphin (Dyn) / kappa-opioid receptor (KOR) system is highly enriched in the mPFC, and its dysregulation is implicated in neuropsychiatric disorders. However, it is unclear how the Dyn / KOR system modulates excitatory and inhibitory circuits that are integral for mPFC information processing and behavioral control. Here, we provide a circuit-based framework wherein mPFC Dyn / KOR signaling regulates excitation-inhibition balance by toggling which afferents drive mPFC neurons. Dyn / KOR regulation of afferent inputs is pathway-specific. Dyn acting on presynaptic KORs inhibits glutamate release from afferent inputs to the mPFC, including the basolateral amygdala (BLA), paraventricular nucleus of the thalamus, and contralateral cortex. The majority of excitatory synapses to mPFC neurons, including those from the ventral hippocampus (VH), do not express presynaptic KOR, rendering them insensitive to Dyn / KOR modulation. Dyn / KOR signaling also suppresses afferent-driven recruitment of specific inhibitory sub-networks, providing a basis for Dyn to disinhibit mPFC circuits. Specifically, Dyn / KOR signaling preferentially suppresses SST interneuron- relative to PV interneuron-mediated inhibition. Selective KOR action on afferents or within mPFC microcircuits gates how distinct limbic inputs drive spiking in mPFC neurons. Presynaptic Dyn / KOR signaling decreases KOR-positive input-driven (e.g. BLA) spiking of mPFC neurons. In contrast, KOR-negative input recruitment of mPFC neurons is enhanced by Dyn / KOR signaling via suppression of mPFC inhibitory microcircuits. Thus, by acting on distinct circuit elements, Dyn / KOR signaling shifts KOR-positive and negative afferent control of mPFC circuits, providing mechanistic insights into the role of neuropeptides in shaping mPFC function. Together, these findings highlight the utility of targeting the mPFC Dyn / KOR system as a means to treat neuropsychiatric disorders characterized by dysregulation in mPFC integration of long-range afferents with local inhibitory microcircuits.

Dataset Information

The Impact of Structural Heterogeneity on Excitation-Inhibition Balance in Cortical Networks.

Publications

The Impact of Structural Heterogeneity on Excitation-Inhibition Balance in Cortical Networks.

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