Postnatal maturation of GABAergic modulation of sensory inputs onto lateral amygdala principal neurons

Abstract

Key pointsr Throughout life, fear learning is indispensable for survival and neural plasticity in the lateral amygdala underlies this learning and storage of fear memories.r During development, properties of fear learning continue to change into adulthood, but currently little is known about changes in amygdala circuits that enable these behavioural transitions.r In recordings from neurons in lateral amygdala brain slices from infant up to adult mice, we show that spontaneous and evoked excitatory and inhibitory synaptic transmissions mature into adolescence.r At this time, increased inhibitory activity and signalling has the ability to restrict the function of excitation by presynaptic modulation, and may thus enable precise stimulus associations to limit fear generalization from adolescence onward.r Our results provide a basis for addressing plasticity mechanisms that underlie altered fear behaviour in young animals.Abstract Convergent evidence suggests that plasticity in the lateral amygdala (LA) participates in acquisition and storage of fear memory. Sensory inputs from thalamic and cortical areas activate principal neurons and local GABAergic interneurons, which provide feed-forward inhibition that tightly controls LA activity and plasticity via pre-and postsynaptic GABA A and GABA B receptors. GABAergic control is also critical during fear expression, generalization and extinction in adult animals. During rodent development, properties of fear and extinction learning continue to change into early adulthood. Currently, few studies have assessed physiological changes in amygdala circuits that may enable these behavioural transitions. To obtain first insights, we investigated changes in spontaneous and sensory input-evoked inhibition onto LA principal neurons and then focused on GABA B receptor-mediated modulation of excitatory sensory inputs in infant, juvenile, adolescent and young adult mice. We found that spontaneous and sensory-evoked inhibition increased during development. Physiological changes were accompanied by changes in dendritic morphology. While GABA B heteroreceptors were functionally expressed on sensory afferents already early in development, they could only be physiologically recruited by sensory-evoked GABA release to mediate heterosynaptic inhibition from adolescence onward. Furthermore, we found GABA B -mediated tonic inhibition of sensory inputs by ambient GABA that also emerged in adolescence. The observed increase in GABAergic drive may be a substrate for providing modulatory GABA. Our data suggest that GABA B -mediated tonic and evoked presynaptic inhibition can suppress sensory input-driven excitation in the LA to enable precise stimulus associations and limit generalization of conditioned fear from adolescence onward.

Age-dependent regulation of GABA transmission by kappa opioid receptors in the basolateral amygdala of Sprague-Dawley rats

“…Furthermore, different internal solutions can also alter intracellular enzymatic activity, such as protein kinase A (Vargas et al, 1999). Another more likely possibility is that adult BLA pyramidal neurons have a more complex dendritic arborization and/or spine density (Bosch and Ehrlich, 2015), which could be better detected with the K-gluconate internal. While the reasons for this observation are not clear, these data suggest that differences in ion channels/conductances may exist in BLA pyramidal neurons across development.…”

Effects of Repeated Stress on Age-Dependent GABAergic Regulation of the Lateral Nucleus of the Amygdala

“…It is unclear why blockade of GABA receptors does not cause an increase in the number of active LAT neurons in adult rats (although there is a trend in this direction). Possible explanations may include additional sources of regulation (eg greater contribution of h channels, SK channels, GABA b receptors; Ehrlich et al, 2012;Bosch and Ehrlich, 2015) that suppress neuron firing even when GABA A receptors are blocked.…”

The basolateral amygdala γ‐aminobutyric acidergic system in health and disease

“…In other words, the contribution of PPD by GABA B receptors may be due primarily to activation of GABA B receptors in infancy, whereas PPD in older animals is only partially controlled by GABA B receptors. Moreover, Bosch and Ehrlich () found that presynaptic GABA B receptors, which are present on sensory inputs to LA principal neurons, are activated as early as P8. Finally, tonic presynaptic control of IPSCs and excitatory postsynaptic currents (EPSCs) in the LA appears to be mediated by GABA B receptors and is likely permitted by ambient GABA that also emerge in adolescence (Bosch and Ehrlich, ).…”