Development of neuronal circuits involves a period during which synaptic connectivity is dynamically refined to its adult functions in an activity-dependent manner. During this early development, immature neuronal networks are highly susceptible for Hebbian and homeostatic plasticity, which is instrumental for the development of the circuitry, but also makes them highly vulnerable to disturbance.
We aim to understand the synaptic mechanisms that facilitate structural and functional plasticity in the developing circuits, focusing on glutamate-receptor mediated signaling in the hippocampus and amygdala. In addition, we are interested to understand how malfunction of these early plasticity mechanisms influences wiring of the limbic networks and increase vulnerability to neuropsychiatric disorders later on in life. In this context, we are particularly interested in the effects of early life stress.
Our experimental approach involves the use of electrophysiological techniques in combination with pharmacological and local genetic manipulation in various neuronal preparations.
Development of limbic neural circuits is regulated by kainate-type glutamate receptors
Kainate receptors (KARs), together with AMPA and NMDA receptors, belong to the family of ionotropic glutamate receptors. We and others have shown that KARs have unique developmentally restricted functions that are downregulated in parallel with maturation of the circuitry (for review, see Lauri et al., 2021). These immature-type KAR functions are critical for activity –dependent refinement of the synaptic circuitry, both in the hippocampus and in the amygdala.
GluA4 – subunit containing AMPA receptors facilitate plasticity at immature synapses
The AMPA receptor subunit GluA4 is transiently expressed in hippocampal CA1 principal neurons at the time synaptic connectivity is forming. Our research supports that GluA4 subunit confers a minimal mechanism for activity-dependent AMPA-receptor regulation to facilitate plasticity during early development of glutamatergic synapses.
Our recent results show that chronic stress associates with loss of kainate receptor expression in parvalbumin – type interneurons (PV IN) in amygdala, which contributes to stress-induced PV IN malfunction and hyperexcitability of the amygdala principal neurons.