Abstract
Cortical networks display persistent activity in the form of periods of sustained synchronous depolarizations (‘UP states’) punctuated by periods of relative hyperpolarization (‘DOWN states’), which together form the slow oscillation. UP states are known to be synaptically generated and are sustained by a dynamic balance of excitation and inhibition, with fast ionotropic glutamatergic excitatory and GABAergic inhibitory conductances increasing during the UP state. Previously, work from our group demonstrated that slow metabotropic GABA receptors also play an important role in terminating the UP state, but the effects of other neuromodulators on this network phenomenon have received little attention. Given that persistent activity is a neural correlate of working memory and that signalling through dopamine receptors has been shown to be critical for working memory tasks, we examined whether dopaminergic neurotransmission affected the slow oscillation. Here, using an in vitro model of the slow oscillation in rat medial entorhinal cortex, we showed that dopamine strongly and reversibly suppressed cortical UP states. We showed that this effect was mediated through D1-like and not D2-like dopamine receptors, and we found no evidence that tonic dopaminergic transmission affected UP states in our model.
Highlights
Neuronal networks display persistent activity, an important form of circuit dynamics thought to underlie phenomena such as working memory
One example of persistent activity is seen during the slow oscillation, where neurons oscillate between periods of sustained depolarization and firing (‘UP states’) punctuated by epochs of hyperpolarization and reduced firing (‘DOWN states’)
We previously reported that fast GABAA receptor-mediated inhibition balances the UP state, whereas slow GABAB receptor-mediated inhibition is important for the termination of the UP state (Mann et al, 2009), but whether other neuromodulators affect the slow oscillation has yet to be determined
Summary
Neuronal networks display persistent activity, an important form of circuit dynamics thought to underlie phenomena such as working memory (reviewed by Major & Tank, 2004). UP and DOWN states (UDS) can be observed using reduced in vitro preparations such as slices containing the visual cortex (Sanchez-Vives & McCormick, 2000) or entorhinal cortex (Cunningham et al, 2006; Mann et al, 2009) Insights from these in vitro studies show that UP states are associated with an increase in both excitatory and that inhibitory neurotransmission (Sanchez-Vives & McCormick, 2000), and that inhibitory conductances dynamically. The mEC forms one of the main input and output systems to the hippocampus (Canto et al, 2008), so persistent activity in the mEC may be involved in cognitive processes such as working memory and spatial navigation. Diffuse neuromodulatory systems, such as dopaminergic projections, might be expected to modulate the persistent activity of UDS in the mEC
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