The blueprint of GABAergic synapses onto GABAergic interneurons: which disinhibitory cortical circuits are laid out in a cortical column?

• Applicant: Professor Dr. Jochen Ferdinand Staiger
• Subject Area: Experimental and Theoretical Network Neuroscience ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2018 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 410546234

Excitation-inhibition balance is a crucial mechanism that is necessary for proper information processing in synaptic circuits of the neocortex (Isaacson and Scanziani, 2011). It is known that different types of GABAergic interneurons establish symmetric synapses on specific subcellular portions of the somatodendritic membrane of excitatory principal neurons, i.e. axo-axonic (or Chandelier) cells on the axon initial segment, basket cells perisomatically and dendrite-targeting interneurons (i.e. Martinotti cells) on various portions of the dendritic tree. However, whether connectivity amongst GABAergic interneurons themselves follows the same wiring rules, is still an open question but we have recently obtained indirect evidence that this might be the case. Furthermore, since inhibition of inhibitory neurons (and thus disinhibition of downstream neurons) is a newly emerging cortical circuit motif, it is important to fully elucidate which types of GABAergic neurons can be presynaptic to which other types. Thus, we want to test for connectivity in an interneuron subtype-specific manner by using optogenetically transduced animals (cre-dependent ChR2-expression in PVcre, SOMcre and VIPcre mouse lines). Most importantly, subsequently we will perform paired whole cell recordings of three main interneuron subpopulations (i.e. basket cells, BC; Martinotti cells, MC; and bipolar/bitufted cells, BPC) contained in these transgenic mouse lines and determine the elementary functional properties of the following pre-post pairs: MC/BC, BPC/BC, with BC finally targeting the perisomatic region of pyramidal cells; BC/BPC, MC/BPC, with BPC finally targeting the intermediate dendritic trees of pyramidal cells; BC/MC, BPC/MC, with MC finally targeting the distal dendritic trees of pyramidal cells. By filling these pairs of neurons with biocytin (or fluorescent dyes) and reconstructing them quantitatively and three-dimensionally, we will be able to trace the axon of the presynaptic cell onto the somatodendritic domain of the postsynaptic neuron. Thus, the number and location of putative synapses will be mapped with Neurolucida software. A subset of these contacts will be verified as synapses in correlated light and electron microscopic preparations. These studies will shed light onto the functional and subcellular structural logic of inhibitory-inhibitory connections. Moreover, insights gained in these ground-laying experiments will guide in vivo approaches directed toward which inputs select which disinhibitory circuit motif and how this is used in sensory information processing for goal-directed behavior.

• DFG Programme: Research Grants