http://nova.newcastle.edu.au/vital/access/services/Feed ${session.getAttribute("locale")} 5 http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6660 Gamma-aminobutyric acid (GABA) is the major inhibitory transmitter in the brain, and its fast effects are mediated by the GABA-A receptor. It is well known, from pharmacological manipulations, that many exogenous agents alter the efficacy of GABA-A receptors. For example, benzodiazepines increase the effect of GABA and some β-carbolines reduce the effect of GABA at these receptors. Increasing the strength of neuronal inhibition can prevent seizures, reduce anxiety and be neuroprotective. There are also endogenous mechanisms that increase efficacy. For example, more GABA-A receptors can be synthesized and inserted into synapses, but this requires up to 1 h or more. On a shorter timescale, GABAergic inhibition can be potentiated by steroids, e.g., allopregnanolone, synthesized de novo in neural tissue or derived from peripheral endocrine organs. The widespread distribution of these neuroactive steroids across the brain suggests an extensive role in short-term neural plasticity. 2010-09-10T02:50:05.067Z ]]> http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:993 Fast inhibitory neurotransmission in the brain is largely mediated by the γ-aminobutyric acid-type A (GABA A) receptor. The 3α,5α-reduced neurosteroids (e.g., allopregnanolone) are the most potent endogenous modulators of the GABA A receptor. Although it is known that 3α,5α-reduced neurosteroid levels change during stress or depression and over the estrus cycle, a basic physiological role consistent with their pharmacological action remains elusive. We used the unique architecture of the auditory midbrain to reveal a role for 3α,5α-reduced eurosteroids in regulating inhibitory efficacy. After blocking the massive GABAergic projection from the dorsal nucleus of the lateral lemniscus (DNLL) to the contralateral central nucleus of the inferior colliculus (ICC) in anesthetized rats, a reactive increase in the efficacy of other inhibitory circuits in the ICC (separable because of the dominant ear that drives each circuit) was demonstrated with physiological measures—singleneuron activity and a neural-population-evoked response. This effect was prevented by blocking 3α,5α-reduced neurosteroid synthesis with a 5α-reductase inhibitor: finasteride. Immunohistochemistry confirmed that the DNLL blockade induced an increase in 3α,5α-reduced neurosteroids in the contralateral ICC. This study shows that when GABAergic inhibition is reduced, the brain compensates within minutes by locally increasing synthesis of neurosteroids, thereby balancing excitatory and inhibitory inputs in complex neural circuits. 2010-04-27T06:43:07.895Z ]]>