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

Key points

• Throughout life, fear learning is indispensable for survival and neural plasticity in the lateral amygdala underlies this learning and storage of fear memories.
• 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.
• 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.
• 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.
• 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.

Abbreviations

BA

basal nucleus of the amygdala

BLA

basolateral complex of the amygdala

CS

conditioned stimulus

LA

lateral nucleus of the amygdala

LTP

long‐term potentiation

PND

postnatal day

PPD

paired‐pulse depression

PPR

paired‐pulse ratio

sEPSC

spontaneous excitatory postsynaptic current

sIPSC

spontaneous inhibitory postsynaptic current

US

unconditioned stimulus