Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors.
To address the role of D1 receptors in the medial prefrontal cortex, we combined pharmacological and genetic manipulations to examine long-term synaptic potentiation (LTP)/long-term synaptic depression (LTD) in brain slices of rats and mice. We found that the D1 antagonist SCH23390 selectively blocked the maintenance but not the induction of LTP in the prefrontal cortex. Conversely, activation of D1 receptors facilitated the maintenance of LTP, and this effect is impaired in heterozygous D1 receptor knockout mice. Low-frequency stimulation induced a transient depression in the medial prefrontal cortex. This depression could be transformed into LTD by coapplication of dopamine. Coapplication of dopamine, however, shows no facilitating effect on LTD in heterozygous D1 receptor knockout mice. These results provide pharmacological and genetic evidence for a role of D1 receptors in the bidirectional modulation of synaptic plasticity in the medial prefrontal cortex. The absence of this modulation in heterozygous knockout mice shows that a dysregulation of dopamine receptor expression levels can have dramatic effects on synaptic plasticity in the prefrontal cortex.
Huang
Yan-You
YY
Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Simpson
Eleanor
E
Kellendonk
Christoph
C
Kandel
Eric R
ER
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D013997:Time Factors
D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D004298:Dopamine