Acute exposure to 25-hydroxy-cholesterol selectively reduces GABAb and not GABAa receptor-mediated synaptic inhibition.
Intracellular recording techniques were used to study the effects of the cholesterol oxide, 25-hydroxycholesterol (25-OH-Chol), on gamma-aminobutyric acid (GABA) receptor-mediated inhibitory postsynaptic potentials (IPSPs) in brain slices of the rat lateral septum. Superfusion of 25-OH-Chol increased the peak amplitude of the GABAa IPSP in more than half of the neurons tested, many of which exhibited a similar increase in the GABAb IPSP. However, some neurons exhibited a gradual decrease in input resistance and a selective reduction or blockade of the GABAb IPSP during prolonged exposure. Cholesterol partly mimicked the effects of 25-OH-Chol. These findings indicate that 25-OH-Chol can selectively reduce or block metabotropic GABAb while sparing ionotropic GABAa receptor-mediated synaptic inhibition. Our results indicate that brain slices can be used to study the effects of short term alterations in cholesterol on the excitability and synaptic integration properties of neurons.
Phelan
K D
KD
Department of Anatomy, University of Arkansas for Medical Sciences, Little Rock 72205, USA.
Mahler
H R
HR
D000818:Animals; D001921:Brain / Q000502:physiology*; D006888:Hydroxycholesterols / Q000494:pharmacology*; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*
D006888:Hydroxycholesterols; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C007997:25-hydroxycholesterol