Dopamine increases the gain of the input-output response of rat prefrontal pyramidal neurons.
Dopaminergic modulation of prefrontal cortical activity is known to affect cognitive functions like working memory. Little consensus on the role of dopamine modulation has been achieved, however, in part because quantities directly relating to the neuronal substrate of working memory are difficult to measure. Here we show that dopamine increases the gain of the frequency-current relationship of layer 5 pyramidal neurons in vitro in response to noisy input currents. The gain increase could be attributed to a reduction of the slow afterhyperpolarization by dopamine. Dopamine also increases neuronal excitability by shifting the input-output functions to lower inputs. The modulation of these response properties is mainly mediated by D1 receptors. Integrate-and-fire neurons were fitted to the experimentally recorded input-output functions and recurrently connected in a model network. The gain increase induced by dopamine application facilitated and stabilized persistent activity in this network. The results support the hypothesis that catecholamines increase the neuronal gain and suggest that dopamine improves working memory via gain modulation.
Thurley
Kay
K
Department of Physiology, University of Bern, Buehlplatz 5, CH-3012 Bern, Switzerland. thurley@pyl.unibe.ch
Senn
Walter
W
Lüscher
Hans-Rudolf
HR
D000818:Animals; D000831:Animals, Newborn; D001552:Benzazepines / Q000494:pharmacology; D003198:Computer Simulation; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D008959:Models, Neurological; D018408:Patch-Clamp Techniques / Q000379:methods; D017397:Prefrontal Cortex / Q000166:cytology*; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D001552:Benzazepines; D018492:Dopamine Antagonists; D004298:Dopamine