Dataset Information

Modulation of prefrontal cortex excitation/inhibition balance rescues social behavior in CNTNAP2-deficient mice.

ABSTRACT: Alterations in the balance between neuronal excitation and inhibition (E:I balance) have been implicated in the neural circuit activity-based processes that contribute to autism phenotypes. We investigated whether acutely reducing E:I balance in mouse brain could correct deficits in social behavior. We used mice lacking the CNTNAP2 gene, which has been implicated in autism, and achieved a temporally precise reduction in E:I balance in the medial prefrontal cortex (mPFC) either by optogenetically increasing the excitability of inhibitory parvalbumin (PV) neurons or decreasing the excitability of excitatory pyramidal neurons. Surprisingly, both of these distinct, real-time, and reversible optogenetic modulations acutely rescued deficits in social behavior and hyperactivity in adult mice lacking CNTNAP2 Using fiber photometry, we discovered that native mPFC PV neuronal activity differed between CNTNAP2 knockout and wild-type mice. During social interactions with other mice, PV neuron activity increased in wild-type mice compared to interactions with a novel object, whereas this difference was not observed in CNTNAP2 knockout mice. Together, these results suggest that real-time modulation of E:I balance in the mouse prefrontal cortex can rescue social behavior deficits reminiscent of autism phenotypes.

SUBMITTER: Selimbeyoglu A

PROVIDER: S-EPMC5723386 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Modulation of prefrontal cortex excitation/inhibition balance rescues social behavior in <i>CNTNAP2</i>-deficient mice.

Selimbeyoglu Aslihan A Kim Christina K CK Inoue Masatoshi M Lee Soo Yeun SY Hong Alice S O ASO Kauvar Isaac I Ramakrishnan Charu C Fenno Lief E LE Davidson Thomas J TJ Wright Matthew M Deisseroth Karl K

Science translational medicine 20170801 401

Alterations in the balance between neuronal excitation and inhibition (E:I balance) have been implicated in the neural circuit activity-based processes that contribute to autism phenotypes. We investigated whether acutely reducing E:I balance in mouse brain could correct deficits in social behavior. We used mice lacking the <i>CNTNAP2</i> gene, which has been implicated in autism, and achieved a temporally precise reduction in E:I balance in the medial prefrontal cortex (mPFC) either by optogene ...[more]

PMID: 28768803

Similar Datasets

Project description:RATIONALE:During value-based decision-making, organisms make choices on the basis of reward expectations, which have been formed during prior action-outcome learning. Although it is known that neuronal manipulations of different subregions of the rat prefrontal cortex (PFC) have qualitatively different effects on behavioral tasks involving value-based decision-making, it is unclear how these regions contribute to the underlying component processes. OBJECTIVES:Assessing how different regions of the rodent PFC contribute to component processes of value-based decision-making behavior, including reward (or positive feedback) learning, punishment (or negative feedback) learning, response persistence, and exploration versus exploitation. METHODS:We performed behavioral modeling of data of rats in a probabilistic reversal learning task after pharmacological inactivation of five PFC subregions, to assess how inactivation of these different regions affected the structure of responding of animals in the task. RESULTS:Our results show reductions in reward and punishment learning after PFC subregion inactivation. The prelimbic, infralimbic, lateral orbital, and medial orbital PFC particularly contributed to punishment learning, and the prelimbic and lateral orbital PFC to reward learning. In addition, response persistence depended on the infralimbic and medial orbital PFC. As a result, pharmacological inactivation of the infralimbic and lateral orbitofrontal cortex reduced the number of reversals achieved, whereas inactivation of the prelimbic and medial orbitofrontal cortex decreased the number of rewards obtained. Finally, using simulated data, we explain discrepancies with a previous study and demonstrate complex, interacting relationships between conventional measures of probabilistic reversal learning performance, such as win-stay/lose-switch behavior, and component processes of value-based decision-making. CONCLUSIONS:Together, our data suggest that distinct components of value-based learning and decision-making are generated in medial and orbital PFC regions, displaying functional specialization and overlap, with a prominent role of large parts of the PFC in negative feedback processing.

Dataset Information

Modulation of prefrontal cortex excitation/inhibition balance rescues social behavior in CNTNAP2-deficient mice.

Publications

Modulation of prefrontal cortex excitation/inhibition balance rescues social behavior in <i>CNTNAP2</i>-deficient mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets