Abstract
Prefrontal cortical activity in primate brain plays a critical role in cognitive processes involving working memory and the executive control of behavior. Groups of prefrontal cortical neurons within specified cortical layers along cortical minicolumns differentially generate inter- and intra-laminar firing to process relevant information for goal oriented behavior. However, it is not yet understood how cocaine modulates such differential firing in prefrontal cortical layers. Rhesus macaque nonhuman primates (NHPs) were trained in a visual delayed match-to-sample (DMS) task while the activity of prefrontal cortical neurons (areas 46, 8 and 6) was recorded simultaneously with a custom multielectrode array in cell layers 2/3 and 5. Animals were reinforced with juice for correct responses. The first half of the recording session (control) was conducted following saline injection and in the second half of the same session cocaine was administered. Prefrontal neuron activity with respect to inter- and intra-laminar firing in layers 2/3 and 5 was assessed in the DMS task before and after the injection of cocaine. Results showed that firing rates of both pyramidal cells and interneurons increased on Match phase presentation and the Match Response (MR) in both control and cocaine halves of the session. Differential firing under cocaine vs. control in the Match phase was increased for interneurons but decreased for pyramidal cells. In addition, functional’ interactions between prefrontal pyramidal cells in layer 2/3 and 5 decreased while intra-laminar cross-correlations in both layers increased. These neural recordings demonstrate that prefrontal neurons differentially encode and process information within and between cortical cell layers via cortical columns which is disrupted in a differential manner by cocaine: administration.
Highlights
The results demonstrate that prefrontal cortical neurons differentially encode and process information within and between layers in the cortical columns in a manner sensitive to alterations provoked by the addicting drug, cocaine
Hand tracking movements of a cursor on the screen were made in the Match phase to select the correct (Sample) image which varied with respect to image-type and screen position on each trial
Recent analyses have shown that animals executed a ‘‘decision process’’ in the Match phase of the task (Figure 1A) involving target selection, described here in relation to neuron firing in prefrontal cortex (PFC) (Opris et al, 2012a,b, 2013)
Summary
Cognitive deficits related to drug addiction, aging, attention deficit hyperactivity disorder (ADHD), schizophrenia and autism are characterized by the inability to select correct behavioral responses for the appropriate environmental or task related circumstances (Shallice and Burgess, 1991; Duncan et al, 1997; Buxhoeveden and Casanova, 2002; Buxhoeveden et al, 2006; Beveridge et al, 2008; Brennan and Arnsten, 2008; Dobbs, 2010; Wang et al, 2011). A common feature of such cognitive deficits in primate brain is the disruption of neural activity in prefrontal cortex (PFC), Disruption of columnar and laminar cognitive processing namely the precise laminar/columnar organization of neural firing that coordinates cognition and behavior (Mountcastle, 1997; Rao et al, 1999; Beveridge et al, 2008; Weiler et al, 2008; Opris et al, 2012a). The results demonstrate that prefrontal cortical neurons differentially encode and process information within and between layers in the cortical columns in a manner sensitive to alterations provoked by the addicting drug, cocaine
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