# Synchronization in Noisy, Heterogeneous Excitatory/Inhibitory Networks

> **NIH NIH R01** · LSU HEALTH SCIENCES CENTER · 2020 · $420,095

## Abstract

Gamma band (30-90 Hz) oscillations are hypothesized to play an important role in normal cognition, including
memory encoding and retrieval, attention and perception. Gamma synchrony is abnormally regulated in many
disorders, such as epilepsy, schizophrenia and dementias such as Alzheimer's disease. Distinct mechanisms
likely underlie gamma oscillations in different brain areas, and mechanisms may also vary within the same
brain area under different conditions. Models of these diverse mechanisms generally assume that interneurons
function as integrators that can fire at arbitrarily low rates (type 1 excitability). In contrast, resonator neurons
have an abrupt threshold at a nonzero minimum firing frequency (type 2 excitability). We have previously
shown that the fast spiking (FS), parvalbumin-positive (PV+) basket cell interneurons in the medial entorhinal
cortex (MEC) are type 2, and exhibit strong resonance and post-inhibitory rebound (PIR). Moreover, our theo-
retical work shows these features enhance the ability to synchronize in heterogeneous, sparsely-connected
noisy networks. Aim 1 will focus on the biophysical basis for PIR and type 2 excitability in FS cells in mouse
MEC and hippocampal area CA3 in vitro. Aim 2 will use models of CA3 and MEC FS cells from Aim 1 embed-
ded in excitatory/inhibitory networks to develop new theory to identify and optimally manipulate the various
mechanisms underlying gamma synchrony. We will analyze different slices of the parameter space to find or-
ganizing principles for distinct gamma mechanisms and how to distinguish between them. We will develop the-
oretical methods to account for the effect of jitter in spike times. This theory may lead to better design of poten-
tial therapies for cognitive deficits. Aim 3 will test the theoretical predictions of optimally gated transitions into
theta-nested gamma in the MEC in vitro using optogenetic control of extrinsic inputs. We will test the hypothe-
ses that both excitatory and inhibitory theta-locked signals can evoke nested gamma oscillations during opto-
genetically-induced theta in the MEC by aligning the phases of the FS interneurons. A consistent reset of the
theta phase of gamma oscillations is required in many coding schemes; we expect that multiple reset mecha-
nisms may be operative in the MEC. Our central hypothesis is that the excitability type of inhibitory interneu-
rons controls the type and robustness of oscillations exhibited in excitatory/inhibitory networks.

## Key facts

- **NIH application ID:** 9914337
- **Project number:** 5R01NS054281-12
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** Carmen Castro Canavier
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $420,095
- **Award type:** 5
- **Project period:** 2005-09-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9914337

## Citation

> US National Institutes of Health, RePORTER application 9914337, Synchronization in Noisy, Heterogeneous Excitatory/Inhibitory Networks (5R01NS054281-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9914337. Licensed CC0.

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