title: The Effects of Guanfacine and Phenylephrine on a Spiking Neuron Model of Working Memory.
abstract: We use a spiking neural network model of working memory (WM) capable of performing the spatial delayed response task (DRT) to investigate 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 through recurrent connections. We reproduce the standard forgetting curve and then show that this curve changes in the presence of GFC and PHE, whose application is simulated by manipulating functional, neural, and biophysical properties of the model. In particular, applying GFC causes increased activity in neurons that are sensitive to the information currently being remembered, while applying PHE leads to decreased activity in these same neurons. Interestingly, these differential 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.
authors.affiliation: Centre for Theoretical Neuroscience, University of Waterloo.
authors.forename: Peter
authors.initials: P
authors.lastname: Duggins
authors.affiliation: Centre for Theoretical Neuroscience, University of Waterloo.
authors.forename: Terrence C
authors.initials: TC
authors.lastname: Stewart
authors.affiliation: Centre for Theoretical Neuroscience, University of Waterloo.
authors.forename: Xuan
authors.initials: X
authors.lastname: Choo
authors.affiliation: Centre for Theoretical Neuroscience, University of Waterloo.
authors.forename: Chris
authors.initials: C
authors.lastname: Eliasmith
mesh_terms: D000818:Animals; D016316:Guanfacine / Q000494:pharmacology*; D000882:Haplorhini; D006801:Humans; D008570:Memory, Short-Term / Q000187:drug effects; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology
chemical_list: D010656:Phenylephrine; D016316:Guanfacine
keywords: ADHD; Delayed response task; Neural Engineering Framework; Pharmacology; Working memory