Acute d-Amphetamine alters the temporal patterning of intermittent synchronized oscillations in hippocampal and prefrontal circuits of the rat

poster abstractD-Amphetamine (d-AMPH) increases the bioavailability of numerous catecholamines, including dopamine, throughout the brain and modulates neural firing in cortical and subcortical regions. While a complex array of d-AMPH-mediated effects on firing have been reported, less is known regarding how d-AMPH affects the oscillatory properties of cortical circuits. In the current study, we simultaneously recorded local field potentials from electrode arrays implanted in the medial prefrontal cortex (PFC) and hippocampus (HC) of awake freely moving rats treated with saline, 1.0 mg/kg, or 3.3 mg/kg d-AMPH. The fine temporal structure of synchrony in delta, theta, beta, and gamma bands between these brain regions was examined to characterize how phase synchronization was altered by each dose of d-AMPH relative to saline. Differences were observed in the average level of phase-locking and in the variation of temporal patterns of synchrony on short (sub-second) time scales (including the distribution of durations of desynchronization events. In general, treatment with d-AMPH evoked higher levels of phase-locking. While this imperfect phase-locking can be potentially attained with both large number of short desynchronization episodes and small number of long desynchronization episodes, the data are marked by the dominance of short desynchronization episodes. These results suggest that within the HC and PFC, d-AMPH acts to increase synchronized oscillatory activity. The dominance of short desynchronization episodes suggests that the synchrony can be easily destabilized, yet it can be quickly re-established. The ease with which neural circuits can transition between synchronized and desynchronized dynamics may reflect altered information transfer regimes in these circuits and contribute to the spectrum of effects on cognition frequently observed with d-AMPH

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

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