Interaction of GABAA-receptor function and network activity in the developing hippocampus

• Applicants: Professor Dr. Knut Holthoff; Professor Dr. Knut Kirmse
• Subject Area: Experimental and Theoretical Network Neuroscience ; Developmental Neurobiology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 442107075

The developing hippocampus displays correlated network activity that is supposed to be important for the maturation of neuronal memory circuits. In newborn mice during the first week after birth, hippocampal network activity is strongly driven by tactile and proprioceptive feedback signals resulting from self-generated muscle twitches. Building on findings from the first funding period, we here examine the hypothesis that mutual interactions between correlated network activity and GABAergic signaling instruct the development of hippocampal neuronal circuits in vivo. Using three-dimensional two-photon Ca2+ imaging, we will first investigate how somatosensory input is represented at the single-cell level in GABAergic and glutamatergic neurons of area CA1 before eye opening. Bidirectional modulation of neuronal activity by chemo- and optogenetic approaches will then be applied to dissect the role of GABAergic interneurons in the encoding of somatosensory information by pyramidal cells. Functional analyses will be complemented by mapping the anatomical connectivity between the somatosensory cortex and the entorhinal-hippocampal formation using viral tracers and brain-wide two-photon tomography at single-cellular resolution. Silencing cortico-hippocampal network activity at different postnatal stages will enable us to elucidate its long-term developmental significance for the proper maturation of synaptic, connectomic and network dynamical properties.

• DFG Programme: Research Grants