Critical role of the prefrontal cortex in the regulation of hippocampus-accumbens information flow.
The nucleus accumbens (NAc) is an integral part of limbic circuits proposed to play a central role in the pathophysiology of schizophrenia, and is positioned to integrate information from limbic and cortical regions, including the medial prefrontal cortex (mPFC) and the hippocampus. The ventral subiculum (vSub) of the hippocampus, in particular, is proposed to gate information flow within the NAc, a factor that is disrupted in models of schizophrenia. Using in vivo extracellular recordings in anesthetized rats, we examined the response of NAc neurons to vSub stimulation and how this is modulated by the mPFC. We found that inactivation of mPFC by tetrodotoxin attenuates the ability of the vSub to drive spike firing in the NAc. Thus, a contribution of the mPFC is required for the activation of NAc by the vSub. However, when long-term potentiation is induced in the vSub-NAc pathway, the vSub is now capable of driving the NAc without the participation of the mPFC. Moreover, this interaction is dependent on activation of dopaminergic D(2) receptors in the NAc. This work demonstrates the critical role of the mPFC in the ability of vSub to drive NAc neurons in normal anesthetized animals. One model of schizophrenia posits that vSub hyperactivity may underlie both the hyperdopaminergic state and disruption of information flow in this circuit in schizophrenia. Therefore, inactivation of the mPFC, as would occur with mPFC leukotomy in schizophrenia, may prevent the abnormal vSub drive of the NAc.
Belujon
Pauline
P
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. belujon@pitt.edu
Grace
Anthony A
AA
D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D018492:Dopamine Antagonists; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013469:Sulpiride / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D018492:Dopamine Antagonists; D013779:Tetrodotoxin; D013469:Sulpiride