FBS Colloquia No.222KOKORO-Biology Group
| Seminar or Lecture |
Classification of parvalbumin-positive inhibitory neurons by a difference of local microcircuits and relation with clustered protocadherin gamma Nanami Kawamura [KOKORO-Biology Group] Visualization of the homophilic interaction between clustered protocadherins Natsumi Hoshino [KOKORO-Biology Group] |
|---|---|
| Date and Time | Thursday, September 19, 2019, 12:15-13:00 |
| Place | 2F Seminar Room, BioSystems Building |
| Language | Japanese |
| Contact |
Takashi Kitsukawa |
Classification of parvalbumin-positive inhibitory neurons by a difference of local microcircuits and relation with clustered protocadherin gamma
The specificity of synaptic connections in the sensory cortex is fundamental for the proper processing of sensory information. Excitatory and fast-spiking inhibitory neurons form neural networks on the basis of the specific synaptic connections in the rat visual cortex. However, the molecular mechanisms of the formation of specific neural connections between excitatory and inhibitory cortical neurons have not been elucidated yet. Our previous study has shown that reciprocal connections formed preferentially between clonally-related excitatory neurons are significantly decreased by the deletion of clustered protocadherins (cPcdhs) in the mouse barrel cortex, indicating that cPcdhs are involved in the formation of specific neuronal connections in the cerebral cortex. In mice, 58 cPcdh genes, which encode the cell-adhesion membrane protein cPcdhs, are organized into three gene clusters, α, β and γ. Individual neurons express distinct combinations of these isoforms. In this study, we investigated whether cPcdhγ is involved in the formation of the neural connections between excitatory and parvalbumin (PV) positive inhibitory cells by triple whole-cell patch clamp recording. We found the two types of PV cells according to the connectivity with pyramidal cells in control mice. One type of PV cells formed exclusively reciprocal connections with pyramidal cells, and the other received less excitatory inputs resulting in the low-reciprocity. However, the specificity was impaired by the deletion of cPcdhγ, indicating that cPcdhγ is involved in the specific neural connections between excitatory and inhibitory neurons.
Visualization of the homophilic interaction between clustered protocadherins
Neural networks are formed by specific synaptic connections between neurons. In the formation of neural networks, cell surface molecules play an important role in the recognition of appropriate targets. One potential candidate of such cell surface molecules is the clustered protocadherin (cPcdh), which consists of 58 isoforms. The cPcdh is an adhesion molecule that adheres specifically between cells that express the same cPcdh isoforms via trans homophilic interactions. However, due to the technical difficulty in detecting the homophilic interaction of cPcdhs, the location and timing of cPcdhs when functioning as recognition molecules has not yet been elucidated. To overcome this difficulty, I focus on visualizing the cPcdh interaction in living cells. To this end, we have developed the cPcdh molecule that can visualize the binding state by Forster resonance energy transfer (FRET). In this seminar, I will discuss the property of the cPcdh homophilic interaction revealed by the assay using K562 cells. Also, I would like to talk about the challenge to observe the cPcdh homophilic interaction using neurons.
