Structural change of GABAA receptors during early development in the visual cortex

King's College London (2005) J Physiol 565P, PC60

Communications: Structural change of GABAA receptors during early development in the visual cortex

Morales, Bernardo ; Rozas, Carlos ; Encina, Marlene ; Zeise, Marc ; Pancetti, Floria ;

1. Neuroscience Lab, Department of Biology, University of Santiago of Chile, Santiago, Chile.

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Experience induces profound functional and structural modifications in the visual cortex neuronal circuits. These modifications occurs in the early postnatal life, during a brief period of time called critical period. Long-term potentiation (LTP) and long-term depression (LTD) have been proposed as models by which this plasticity occur. Similar to the ocular dominance, the induction of LTP and LTD in rats have critical periods of around 5 weeks, however the cellular and molecular mechanisms that initiate and eventually end this critical period are still controversial. We show evidence that the maturation of GABAergic circuits, which also reaches a maximum in the 5th week, plays an important role in establishing the end of the critical period for the induction of synaptic plasticity in visual cortex. Slices of 300 μm thick were obtained from 3-8 week-old Long evans rats, killed by decapitation under halothane anesthesia according with the guidelines of the Ethics Committee of the University of Santiago, and maintained in artificial cerebrospinal fluid for 1 hr before recording. GABAergic whole cell currents evoked with protocols of 15 repetitive stimuli between 1 to 50 Hz, applied to layer 4, were recorded from layer 2/3 under symmetric Cl- conditions. Field post-synaptic excitatory potentials were evoked by electrical stimulation with bipolar electrodes localized on the white matter and recorded from layer 2/3. LTP or LTD were induced either after tetanic or low frequency stimulation, respectively. After the electrophysiological experiments, the slices were frozen and analyzed by inmunoblotting for the presence of GABAA receptor subunits. The results obtained at -80 mV in the presence of 20 μM CNQX and 100 μM APV to block fast glutamatergic transmission, show that IPSCs recorded in cells from 3 weeks old rats became depressed during the train. The peak response amplitude rapidly decreased, reaching a steady level by the 10th pulse. The maximal attenuation in pyramidal neurons from 5 week old rats (0.49±0.05%, n=14) was significantly smaller than in 3 week old animals (0.32±0.04%, n=12; Mann-Whitney U test, Z=-3.36, P<0.001). It was also observed that there is a decrease in the amplitude of LTP (Z=1.98, P<0.05) and LTD (Z=-1.96, P<0.05) that correlates with age, being easier to induce plasticity in 3 week old rats than in rats older than 5 weeks. Interestingly, we found that both effects are correlated with a structural change of the GABAA receptor during development. The expression of GABAA receptor ?2 subunit is higher in 3 week old than in 5, 6 and 8 weeks old rats. The evidence suggests that the GABAergic currents are important in establishing the critical period for plasticity in the visual cortex and this could be in part due to structural changes of the GABAA receptor subunits.



Where applicable, experiments conform with Society ethical requirements.

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