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Amphetamine Exerts Dose-Dependent Changes in Prefrontal Cortex Attractor Dynamics during Working Memory.

Lapish, C.C., Balaguer-Ballester, E., Seamans, J.K., Phillips, A.G. and Durstewitz, D., 2015. Amphetamine Exerts Dose-Dependent Changes in Prefrontal Cortex Attractor Dynamics during Working Memory. Journal of Neuroscience, 35 (28), 10172 - 10187 .

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DOI: 10.1523/JNEUROSCI.2421-14.2015


Modulation of neural activity by monoamine neurotransmitters is thought to play an essential role in shaping computational neurodynamics in the neocortex, especially in prefrontal regions. Computational theories propose that monoamines may exert bidirectional (concentration-dependent) effects on cognition by altering prefrontal cortical attractor dynamics according to an inverted U-shaped function. To date, this hypothesis has not been addressed directly, in part because of the absence of appropriate statistical methods required to assess attractor-like behavior in vivo. The present study used a combination of advanced multivariate statistical, time series analysis, and machine learning methods to assess dynamic changes in network activity from multiple single-unit recordings from the medial prefrontal cortex (mPFC) of rats while the animals performed a foraging task guided by working memory after pretreatment with different doses of d-amphetamine (AMPH), which increases monoamine efflux in the mPFC. A dose-dependent, bidirectional effect of AMPH on neural dynamics in the mPFC was observed. Specifically, a 1.0 mg/kg dose of AMPH accentuated separation between task-epoch-specific population states and convergence toward these states. In contrast, a 3.3 mg/kg dose diminished separation and convergence toward task-epoch-specific population states, which was paralleled by deficits in cognitive performance. These results support the computationally derived hypothesis that moderate increases in monoamine efflux would enhance attractor stability, whereas high frontal monoamine levels would severely diminish it. Furthermore, they are consistent with the proposed inverted U-shaped and concentration-dependent modulation of cortical efficiency by monoamines.

Item Type:Article
Additional Information: Received June 13, 2014. Revision received May 9, 2015. Accepted May 10, 2015.
Uncontrolled Keywords:multiple single-unit recordings dopamine neural computation neural dynamics neuromodulation prefrontal cortex
Group:Faculty of Science & Technology
ID Code:22515
Deposited By: Symplectic RT2
Deposited On:28 Sep 2015 14:48
Last Modified:14 Mar 2022 13:53

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