- TRAFFICKING AND FUNCTION OF NMDARs
N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that play a pivotal role in synaptic transmission, plasticity, and brain development. NMDARs are heterotetrameric complexes composed of two GluN1 and two GluN2 subunits. The composition of GluN2 subunits determines the main biophysical properties of the channel as well as the manner in which they are incorporated into synapses. Additionally, the different GluN2 subunits define the interactions with signaling and scaffolding molecules on the cytosolic side, which influence synaptic plasticity or stability. A particularly critical interaction is that of GluN2B with CaMKII, which is necessary for the induction of Long-Term Potentiation (LTP).
We investigate the mechanisms governing the trafficking, subunit composition, and functional integration of NMDARs into synapses. Our research focuses on understanding the distinct macro-complexes formed depending on the GluN2 subunit composition of the receptor and how these complexes contribute to either synaptic plasticity or stability.
- NEURONAL WNT SIGNALING
Wnt signaling is a highly conserved signal transduction mechanism essential for the embryonic development of metazoans. In the mature central nervous system of mammals, Wnt signaling remains active, but its functions are less well understood.
Our research has revealed that a novel neuronal Wnt signaling cascade regulates the trafficking of NMDARs to synapses, thereby influencing synaptic plasticity—a cellular and molecular foundation of learning and memory. Beyond synaptic effects, neuronal Wnt signaling also modulates two intrinsic neuronal properties: the resting membrane potential and the resonant frequency, a critical determinant of coordinated oscillatory behavior in neural circuits.
We investigate the cellular and molecular mechanisms activated by Wnt signaling in neurons to understand how these pathways contribute to synaptic function, neuronal properties, and overall circuit dynamics.
- NEUROMODULATION OF NEURONAL INTRINSIC PROPERTIES
The intrinsic properties of neurons, such as their resting membrane potential, firing patterns, and resonance frequencies, play a crucial role in shaping how neurons respond to synaptic inputs and participate in network activity. Neuromodulation, the process by which neurotransmitters and signaling molecules regulate these properties, is essential for adaptive behavior and maintaining circuit stability.
Our research focuses on understanding how neuromodulators like acetylcholine and Wnt influence the intrinsic properties of hippocampal neurons. We are particularly interested in uncovering how these changes affect neuronal output, synaptic integration, and their contributions to broader network dynamics under normal and pathological conditions.
Through a combination of electrophysiology and molecular and cellular biology, we aim to elucidate the cellular mechanisms by which neuromodulators fine-tune intrinsic neuronal properties, ultimately providing insights into their roles in learning, memory, and neurological disorders.
