Abstract

Prefrontal cortical (PFC) activity in the primate brain emerging from minicolumnar microcircuits plays a critical role in cognitive processes dealing with executive control of behavior. However, the specific operations of columnar laminar processing in prefrontal cortex (PFC) are not completely understood. Here we show via implementation of unique microanatomical recording and stimulating arrays, that minicolumns in PFC are involved in the executive control of behavior in rhesus macaque nonhuman primates (NHPs) performing a delayed-match-to-sample (DMS) task. PFC neurons demonstrate functional interactions between pairs of putative pyramidal cells within specified cortical layers via anatomically oriented minicolumns. Results reveal target-specific, spatially tuned firing between inter-laminar (layer 2/3 and layer 5) pairs of neurons participating in the gating of information during the decision making phase of the task with differential correlations between activity in layer 2/3 and layer 5 in the integration of spatial vs. object-specific information for correct task performance. Such inter-laminar processing was exploited by the interfacing of an online model which delivered stimulation to layer 5 locations in a pattern associated with successful performance thereby closing the columnar loop externally in a manner that mimicked normal processing in the same task. These unique technologies demonstrate that PFC neurons encode and process information via minicolumns which provides a closed loop form of “executive function,” hence disruption of such inter-laminar processing could form the bases for cognitive dysfunction in primate brain.

Highlights

  • The prefrontal cortex (PFC) with its privileged position at the top of sensory-motor processing hierarchy (Alexander et al, 1986; Fuster, 2001) has been traditionally viewed as the seat of higher cognitive functions such as working memory and executive control of behavior (Fuster and Alexander, 1971; Funahashi et al, 1989; Miller, 2000)

  • INTER-LAMNAR PROCESSING IN PREFRONTAL CORTEX vs. CLOSING THE LOOP The findings reported here (Figures 2, 3, and 4) are consistent with the idea that neurons in the supra- and infra-granular layers form efficient mini-columnar circuits during Match phase target selection required for effective performance of this DMS task (Swadlow et al, 2002; Pesaran et al, 2008; Resulaj et al, 2009; Buffalo et al, 2011; Opris et al, 2011; Takeuchi et al, 2011)

  • The implementation of the unique multielectrode arrays (MEAs) (Figure 2B) provided the basis for the detailed assessment of inter-laminar correlated firing (Opris et al, 2011) that was validated in multiple recordings of layer 2/3 (L2/3) and layer 5 (L5) cell pairs that yielded similar relations following differential changes in performance-dependent task parameters across animals and sessions (Figures 3D, 4D, and 5D)

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Summary

Introduction

The prefrontal cortex (PFC) with its privileged position at the top of sensory-motor processing hierarchy (Alexander et al, 1986; Fuster, 2001) has been traditionally viewed as the seat of higher cognitive functions such as working memory and executive control of behavior (Fuster and Alexander, 1971; Funahashi et al, 1989; Miller, 2000). Minicolumns in PFC are interconnected to each other through horizontal “long range” projections in layer 2/3 (Kritzer and Goldman-Rakic, 1995), inter-laminar miniloops (Weiler et al, 2008; Takeuchi et al, 2011) and “reverberatory loops” through projections to the subcortical basal ganglia nuclei and thalamus (Alexander et al, 1986). Such “reverberatory loops” combine incoming signals from thalamus in layer 4 and inputs from cortical horizontal projections in layer 2/3, in order to compare inputs to a threshold criterion triggering an output response under specific conditions

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