A therapeutic small molecule enhances γ-oscillations and improves cognition/memory in Alzheimer’s disease model mice

Brain rhythms provide the timing for the recruitment of brain activity required for linking together neuronal ensembles engaged in specific tasks.  The γ-oscillations (30-120 Hz) orchestrate neuronal circuits underlying cognitive processes and working memory. These oscillations are reduced in numerous neurological and psychiatric disorders, including early cognitive decline in Alzheimer’s disease (AD). Here we report on a potent brain-permeable small molecule, DDL-920 that increases γ-oscillations and improves cognition/memory in a mouse model of AD, thus showing promise as a new class of therapeutics for AD. We employed anatomical, in vitro, and in vivo electrophysiological, and behavioral methods to examine the effects of our lead therapeutic candidate small molecule. As a first in CNS pharmacotherapy, our lead molecule acts as a potent, efficacious, and selective negative allosteric modulator (NAM) of the γ-aminobutyric acid type A receptors (GABAARs) most likely assembled from α1β2δ..., , , # A therapeutic small molecule enhances γ-oscillations and improves cognition/memory in Alzheimer’s disease model mice

[https://doi.org/10.5061/dryad.4j0zpc8mw](https://doi.org/10.5061/dryad.4j0zpc8mw)

## Description of the data and file structure

This dataset contains individual data points represented in respective figures. The files with the extension .xlsx are Excel files and represent the data displayed in the graphs from the respective figures indicated in the file names.

Fig2A_B.xlsx has two Sheets. Sheet \"Fig2A\" contains the data displayed in Fig2A representing the tonic GABA current after subtraction of gabazine (-GBZ) normalized by the whole-cell capacitance (cap). The units are A/F. Column A contains the data during the control period, and column B the data during the perfusion of tracazoate (10 uM). The number of cells is 5. Sheet \"Fig2B\" contains the data displayed in Fig2B representing the tonic GABA current after subtraction of gabazine (-GBZ) normalized by the whole-...