Dopamine increases excitability of pyramidal neurons in primate prefrontal cortex.

D A Henze, G R González-Burgos, N N Urban, D A Lewis, G Barrionuevo
Author Information
  1. D A Henze: Department of Neuroscience, Center for Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

Abstract

Dopaminergic modulation of neuronal networks in the dorsolateral prefrontal cortex (PFC) is believed to play an important role in information processing during working memory tasks in both humans and nonhuman primates. To understand the basic cellular mechanisms that underlie these actions of dopamine (DA), we have investigated the influence of DA on the cellular properties of layer 3 pyramidal cells in area 46 of the macaque monkey PFC. Intracellular voltage recordings were obtained with sharp and whole cell patch-clamp electrodes in a PFC brain-slice preparation. All of the recorded neurons in layer 3 (n = 86) exhibited regular spiking firing properties consistent with those of pyramidal neurons. We found that DA had no significant effects on resting membrane potential or input resistance of these cells. However DA, at concentrations as low as 0.5 microM, increased the excitability of PFC cells in response to depolarizing current steps injected at the soma. Enhanced excitability was associated with a hyperpolarizing shift in action potential threshold and a decreased first interspike interval. These effects required activation of D1-like but not D2-like receptors since they were inhibited by the D1 receptor antagonist SCH23390 (3 microM) but not significantly altered by the D2 antagonist sulpiride (2.5 microM). These results show, for the first time, that DA modulates the activity of layer 3 pyramidal neurons in area 46 of monkey dorsolateral PFC in vitro. Furthermore the results suggest that, by means of these effects alone, DA modulation would generally enhance the response of PFC pyramidal neurons to excitatory currents that reach the action potential initiation site.

Grants

  1. MH-10474/NIMH NIH HHS
  2. MH-45156/NIMH NIH HHS
  3. MH-51234/NIMH NIH HHS

MeSH Term

Action Potentials
Animals
Benzazepines
Dopamine
Dopamine Antagonists
Dopamine D2 Receptor Antagonists
Dose-Response Relationship, Drug
Electric Stimulation
In Vitro Techniques
Macaca fascicularis
Male
Nerve Net
Patch-Clamp Techniques
Prefrontal Cortex
Pyramidal Cells
Receptors, Dopamine D1
Sensory Thresholds
Sulpiride

Chemicals

Benzazepines
Dopamine Antagonists
Dopamine D2 Receptor Antagonists
Receptors, Dopamine D1
Sulpiride
Dopamine

Word Cloud

Created with Highcharts 10.0.0PFCDApyramidalneurons3layercellseffectspotentialmicroMexcitabilitymodulationdorsolateralprefrontalcortexcellularpropertiesarea46monkey5responseactionfirstantagonistresultsDopaminergicneuronalnetworksbelievedplayimportantroleinformationprocessingworkingmemorytaskshumansnonhumanprimatesunderstandbasicmechanismsunderlieactionsdopamineinvestigatedinfluencemacaqueIntracellularvoltagerecordingsobtainedsharpwholecellpatch-clampelectrodesbrain-slicepreparationrecordedn=86exhibitedregularspikingfiringconsistentfoundsignificantrestingmembraneinputresistanceHoweverconcentrationslow0increaseddepolarizingcurrentstepsinjectedsomaEnhancedassociatedhyperpolarizingshiftthresholddecreasedinterspikeintervalrequiredactivationD1-likeD2-likereceptorssinceinhibitedD1receptorSCH23390significantlyalteredD2sulpiride2showtimemodulatesactivityvitroFurthermoresuggestmeansalonegenerallyenhanceexcitatorycurrentsreachinitiationsiteDopamineincreasesprimate

Similar Articles

Cited By