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Inhibition of Rac1 in ventral hippocampal excitatory neurons improves social recognition memory and synaptic plasticity

Contact Information

Keywords

APP/PS1 mouse model; LTP; Rac1; social memory; ventral hippocampus

Abstract

Rac1 is critically involved in the regulation of the actin cytoskeleton, neuronal structure, synaptic plasticity, and memory. Rac1 overactivation is reported in human patients and animal models of Alzheimer's disease (AD) and contributes to their spatial memory deficits, but whether Rac1 dysregulation is also important in other forms of memory deficits is unknown. In addition, the cell types and synaptic mechanisms involved remain unclear. In this study, we used local injections of AAV virus containing a dominant-negative (DN) Rac1 under the control of CaMKIIα promoter and found that the reduction of Rac1 hyperactivity in ventral hippocampal excitatory neurons improves social recognition memory in APP/PS1 mice. Expression of DN Rac1 also improves long-term potentiation, a key synaptic mechanism for memory formation. Our results suggest that overactivation of Rac1 in hippocampal excitatory neurons contributes to social memory deficits in APP/PS1 mice and that manipulating Rac1 activity may provide a potential therapeutic strategy to treat social deficits in AD.

Citation

Zhang, H., Ben Zablah, Y., Zhang, H., Liu, A., Gugustea, R., Lee, D., ... & Jia, Z. (2022). Inhibition of Rac1 in ventral hippocampal excitatory neurons improves social recognition memory and synaptic plasticity. Frontiers in Aging Neuroscience, 14, 914491.

DOI

10.3389/fnagi.2022.914491

EWB Constructs:

homeostasis

EWB Measures:

open field test, elevated plus maze, social interaction test, social test

data availability:

Yes

data availability details:

email corresponding author

brain imaging paradigm:

ventral hippocampus

brain region/circuit:

Exclusion Criteria:

N/A

Inclusion Criteria

N/A

Non-EWB Behavioral
Measures:

N/A

First author:

Haiwang Zhang

species:

mouse

sample size:

N/A

study design:

case control

longitudinal data?

No

younger controls?

N/A

interventions:

Reduced Rac1 hyperactivation in hippocampus and examined effect on social recognition memory in AD mice

study population:

N/A

sex (% female):

N/A

ethnicity (%white)

N/A

Age (mean, sd):

3-4 months

biological/Physiological Measures:

N/A

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