Alcohol and the prefrontal cortex

Abstract

The prefrontal cortex occupies the anterior portion of the frontal lobes and is thought to be one of the most complex anatomical and functional structures of the mammalian brain. Its major role is to integrate and interpret inputs from cortical and sub-cortical structures and use this information to develop purposeful responses that reflect both present and future circumstances. This includes both action-oriented sequences involved in obtaining rewards and inhibition of behaviors that pose undue risk or harm to the individual. Given the central role in initiating and regulating these often complex cognitive and behavioral responses, it is no surprise that alcohol has profound effects on the function of the prefrontal cortex. In this chapter, we review the basic anatomy and physiology of the prefrontal cortex and discuss what is known about the actions of alcohol on the function of this brain region. This includes a review of both the human and animal literature including information on the electrophysiological and behavioral effects that follow acute and chronic exposure to alcohol. The chapter concludes with a discussion of unanswered questions and areas needing further investigation.

FIG. 1

Brodmann areas of the human brain. Schematic shows the Brodmann areas of the human brain with those of the prefrontal cortex shaded in orange. From Grays Anatomy.

FIG. 2

Network organization of the PFC. Schematic shows the important connections of the limbic (orbitofrontal) and executive (dorsolateral and cingulate) divisions of the PFC. Abbreviations: HP (hippocampus), NAC (nucleus accumbens), DMS (dorsomedial striatum), DLS (dorsolateral striatum), THAL (thalamus), STN (sub-thalamic nuclei), HYPO (hypothalamus), AMG (amygdala), GPe (globus pallidus-external), VTA (ventral tegmental area), SNc (substantia nigra-compacta), SNr/ GPi (substantia nigra-reticulata/globus pallidus-internal), VP (ventral pallidum).

FIG. 3

Up-states in PFC slice cultures are inhibited by ethanol. Panel A shows arrangement of prefrontal cortex (PFC), hippocampus (HP), and ventral tegmental area (VTA) in brain slice co-culture. Picture shows dopamine neurons stained for tyrosine hydroxylase (TH). Panel B shows example of up-states recorded from a deep-layer PFC pyramidal neuron. Ethanol reversibly inhibits up-state activity at a concentration of 25 mM (panel D) but not 10 mM (panel C). Taken from Tu et al. (2007).

FIG. 4

Acute ethanol inhibits NMDA but not AMPA-mediated EPSCs in PFC pyramidal neurons. Left panels (A–C) show lack of significant effect of ethanol on AMPA-mediated EPSCs from deep-layer PFC pyramidal neurons. Right panels (A–C) shows that ethanol inhibits NMDA-mediated EPSCs from deep-layer PFC pyramidal neurons. Taken from Weitlauf and Woodward, 2008.

FIG. 5

Ethanol inhibits spike firing of PFC neurons in vivo. Panel A shows the arrangement of multi-electrode array and location in the brain. Panel B shows effects of saline or ethanol on spike firing of PFC neurons. Panel C demonstrates that ethanol inhibits PFC firing in a dose-dependent manner and is correlated with blood ethanol concentration (BEC). Taken from Tu et al. (2007).