McGaughy JA, Koene R, Eichenbaum HB, Hasselmo ME (2004) Effects of cholinergic deafferentation of prefrontal cortex on working memory: A convergence of behavioral and modeling results. Neuroscience 2004 Abstracts 551.7. Society for Neuroscience, San Diego, CA.
Summary: In humans, the prefrontal and medial temporal lobe areas are differentially activated during working memory dependent upon the whether stimuli are familiar or novel. Prefrontal activation occurs with highly familiar stimuli whereas the medial temporal lobe is activated by novel stimuli (Stern, et al. Hippocampus v. 11, 2001). The maintenance of novel information in the entorhinal cortex (EC) is hypothesized to depend upon self-sustained spiking activity in single neurons produced by cholinergic activation of muscarinic receptors (Klink and Alonso, J. Neurophys. 77, 1997). The current study investigated whether cholinergic modulation of the prefrontal cortex regulates sustained spiking activity for familiar stimuli. Rats were trained in an odor-cued delayed non-matching to sample task. After reaching asymptotic performance, rats were infused bilaterally with either 192 IgG-saporin (SAP) or its vehicle into the prefrontal cortex(PFC;0.01μg/μl;1.0μl/injection). Following PFC-SAP lesions,rats were impaired in working memory with highly familiar odors when choice stimuli were probed sequentially but not simultaneously. Though PFC-SAP rats reliably sampled both choices, they failed if the first cup probed matched the sample. PFC-SAP rats were also unable to maintain multiple items in memory. These impairments cannot be explained by the loss of response inhibition, the conditional response rule, attentional or sensory abilities. It is hypothesized that in the absence of a functional frontal cortex, the PFC-SAP rats relied on the EC. Computational modeling of EC suggests repetitions of an odor or the presentations of multiple odors disrupt the pattern of self-sustained spiking in this area and, thus, the representation of the stimulus. These data elucidate the interplay between the PFC and EC during a working memory task.
Related Products: 192-IgG-SAP (Cat. #IT-01)