Memory-enhancing intra-basolateral amygdala clenbuterol infusion reduces post-burst afterhyperpolarizations in hippocampal CA1 pyramidal neurons following inhibitory avoidance learning

Abstract

Activation of the basolateral amygdala can modulate the strength of fear memories, including those in single-trial inhibitory avoidance (IA) tasks. Memory retention, measured by the latency to re-enter a dark-compartment paired 24h earlier with a footshock, varies with intensity of this aversive stimulus. When higher intensity footshocks were used, hippocampal CA1 pyramidal neurons exhibited reduced afterhyperpolarizations (AHPs) 24h post-trial, an effect blocked by immediate post-trial inactivation of the basolateral complex of the amygdala (BLA). Similar AHP reductions in CA1 have been observed in a number of learning tasks, with time courses appropriate to support memory consolidation. When less intense footshocks were used for IA training of Sprague-Dawley rats, immediate post-trial infusion of the β-adrenergic agonist clenbuterol into BLA was required to enhance hippocampal Arc protein expression 45min later and to enhance memory retention tested 48h later. Here, using Long-Evans rats and low-intensity footshocks, we confirmed that bilateral immediate post-trial infusion of 15ng/0.5μl of the β-adrenergic agonist clenbuterol into BLA significantly enhances memory for an IA task. Next, clenbuterol was infused into one BLA immediately post-training, with vehicle infused into the contralateral BLA, then hippocampal CA1 neuron AHPs were assessed 24h later. Only CA1 neurons from hemispheres ipsilateral to post-trial clenbuterol infusion showed learning-dependent AHP reductions. Excitability of CA1 neurons from the same trained rats, but from the vehicle-infused hemispheres, was identical to that from untrained rats receiving unilateral clenbuterol or vehicle infusions. Peak AHPs, medium and slow AHPs, and accommodation were reduced only with the combination of IA training and unilateral BLA β-receptor activation. Similar to previous observations of BLA adrenergic memory-related enhancement of Arc protein expression in hippocampus, increased CA1 neuronal excitability in the fear-modulated IA task was activated by immediate post-trial β-receptor activation of the ipsilateral BLA.