Effects of Guanfacine and Phenylephrine on a Spiking Neuron Model of Working Memory

We utilize a spiking neural network model of working memory (WM) capable of performing the spatial delayed response task (DRT) to investigate the functional effects of two drugs that affect WM: guanfacine (GFC); and phenylephrine (PHE). In this model, the loss of information over time results from changes in the spiking neural activity due to recurrent connections. We reproduce the standard forgetting curve, then show that this curve changes in the presence of GFC and PHE, whose application is simulated by manipulating various neuron properties. In particular, applying GFC causes increased firing in neurons that are sensitive to the information currently being remembered, while applying PHE leads to decreased firing in these same neurons. Interestingly, these memory-specific effects emerge from network-level interactions, because GFC and PHE affect all neurons equally. We compare our model to both electrophysiological data from neurons in monkey dorsolateral prefrontal cortex and to behavioral evidence from monkeys performing the DRT.