Effects of ethanol on persistent activity and up-States in excitatory and inhibitory neurons in prefrontal cortex.
BACKGROUND
Elucidating mechanisms that underlie the neural actions of ethanol is critical for understanding how this drug affects behavior. Increasing evidence suggests that, in addition to mid-brain dopaminergic regions, higher cortical structures play an important role in the pathophysiology associated with alcohol abuse. Previous studies from this laboratory used a novel slice co-culture system to demonstrate that ethanol reduces network-dependent patterns of activity in excitatory pyramidal neurons of the prefrontal cortex (PFC). In the present study, we examine the effect of ethanol on the activity of fast-spiking (FS) interneurons, a sub-population of neurons critically involved in shaping cortical activity.


METHODS
Slices containing the dorsolateral PFC were prepared from neonatal C57 mice and maintained in culture. After 2 to 3 weeks in vitro, whole-cell patch-clamp electrophysiology was used to monitor spontaneous episodes of persistent activity in prelimbic PFC neurons. In some experiments, the use-dependent NMDA receptor blocker, MK801, was included in the pipette recording solution to assess the contribution of NMDA receptors to up-states.


RESULTS
MK801 reduced up-state amplitude and revealed underlying fast EPSPs in excitatory pyramidal neurons while having little effect on these parameters in FS interneurons. Despite this difference, ethanol (44 mM), significantly reduced up-state duration and up-state area in both pyramidal and FS interneurons.


CONCLUSIONS
These results suggest that ethanol reduces the activity of FS interneurons due to disruption of network-dependent activity. This would be expected to further impair the ability of PFC networks to carry out their normal function and may contribute to the adverse effects of ethanol on PFC-dependent behaviors.
Woodward
John J
JJ
Department of Neurosciences and Center for Drug and Alcohol Programs, Medical University of South Carolina, Charleston, SC 29425, USA. woodward@musc.edu
Pava
Matthew J
MJ
D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D018920:Coculture Techniques; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology; D000431:Ethanol / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016202:N-Methylaspartate / Q000502:physiology; D009474:Neurons / Q000187:drug effects*; D009924:Organ Culture Techniques; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D002492:Central Nervous System Depressants; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate