Electrophysiological and Immunohistochemical Evidence for an Increase in GABAergic Inputs and HCN Channels in Purkinje Cells that Survive Developmental Ethanol Exposure

Cerebellum. 2015 Aug;14(4):398-412. doi: 10.1007/s12311-015-0651-2.


Ethanol exposures during the early postnatal period of the rat result in significant death of Purkinje cells (PCs). The magnitude, time-course, and lobular specificity of PC death have been well characterized in several studies. Additionally, significant reduction of climbing fiber inputs to the surviving PCs has been characterized. This study investigates whether further alterations to the cerebellar cortical circuits might occur as a result of developmental ethanol exposures. We first examined the firing pattern of PCs in acute slice preparations on postnatal days 13-15. While the basic firing frequency was not significantly altered, PCs from rat pups treated with ethanol on postnatal days 4-6 showed a significantly increased number of inhibitory postsynaptic potentials (IPSCs) and a larger Ih current. We conducted immunofluorescent studies to identify the probable cause of the increased IPSCs. We found a significant 21 % increase in the number of basket cells per PC and a near doubling of the volume of co-localized basket cell axonal membrane with PC. In addition, we identified a significant (~147 %) increase in HCN1 channel volume co-localized to PC volume. Therefore, the cerebellar cortex that survives targeted postnatal ethanol exposure is dramatically altered in development subsequent to PC death. The cerebellar cortical circuit that results is one that operates under a significant degree of increased resting inhibition. The alterations in the development of cerebellar circuitry following ethanol exposure, and the significant loss of PCs, could result in modifications of the structure and function of other brain regions that receive cerebellar inputs.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / drug effects
  • Age Factors
  • Animals
  • Animals, Newborn
  • Biophysical Phenomena / drug effects
  • Calbindin 1 / metabolism
  • Cell Count
  • Central Nervous System Depressants / pharmacology*
  • Cerebellum / cytology
  • Ethanol / pharmacology*
  • Female
  • Gene Expression Regulation, Developmental / drug effects
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / metabolism*
  • In Vitro Techniques
  • Male
  • Pregnancy
  • Purkinje Cells / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • gamma-Aminobutyric Acid / metabolism*


  • Calbindin 1
  • Central Nervous System Depressants
  • Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
  • Ethanol
  • gamma-Aminobutyric Acid