Post-pubertal emergence of prefrontal cortical up states induced by D1-NMDA co-activation.
Dopamine-glutamate interactions may contribute to persistent electrical activity in the prefrontal cortex (PFC). We tested whether a D1 modulation of NMDA function can result in persistent depolarization in vitro. D1-NMDA co-activation yielded depolarizing plateaus resembling in vivo up states in PFC pyramidal neurons recorded in slices from adult (PD 45-65), but not pre-pubertal (PD 29-38) rats. These plateaus required intracellular Ca2+, activation of L-type Ca2+ channels and protein kinase A. These events were eliminated by intracellular administration of the voltage-gated Na+ channel blocker QX-314 or by interrupting synaptic activity with bath application of tetrodotoxin or the AMPA antagonist CNQX, suggesting that they require both intrinsic and synaptic mechanisms. These recurrent depolarizations could constitute important elements in cortical information processing, allowing synaptic plasticity and memory functions. Acquiring these PFC D1-NMDA interactions after puberty may be a critical element for developing mature cognitive abilities.
Tseng
Kuei Y
KY
Center for Neuropharmacology and Neuroscience, 47 New Scotland Avenue, Albany Medical College (MC-136), Albany, New York 12208, USA. tsengky@mail.amc.edu
O'Donnell
Patricio
P
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D015640:Ion Channel Gating / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009434:Neural Pathways / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012741:Sexual Maturation / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology
D020746:Calcium Channels, L-Type; D018491:Dopamine Agonists; D018690:Excitatory Amino Acid Agonists; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D016202:N-Methylaspartate; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D017868:Cyclic AMP-Dependent Protein Kinases