Rewiring mechanism of neuronal circuits in the central nervous system
Neural circuits are dramatically refined under the influence of external environments and experiences during development. This plasticity is considered to be closely related to the acquisition of language, vision, and absolute pitch during development. The elimination of early-formed redundant synapse is a fundamental process for this developmental refinement of neuronal circuits. Interestingly, even though neural circuits have reached full maturity, the rewiring of circuits can occur again after deafferentation such as the limb amputation. Synapses in the sensory thalamus are known to undergo these synaptic rewirings during postnatal development and deafferentation. We examine the regulation of synaptic function under the synaptic remodeling in the somatosensory system using a combination of tools in vivo and in vitro, including electrophysiological and imaging techniques, as well as genetically manipulated mice.
Mechanisms underlying postnatal development of somatosensory synapses
Sensory information from whiskers, which is one of the major sensory inputs for rodents, is sent to the VPm nucleus in the thalamus via the trigeminal nuclei and through medial lemniscal fibers. The medial lemniscal fibers terminated on VPm neurons undergo massive pruning during development. A VPm neuron first receives synaptic inputs from multiple lemniscal fibers then most of them are eliminated except for a single fiber. This process is modulated by sensory experience so it may be related to neuronal activity which reflects surrounding environment. We explore mechanisms of this synapse pruning of lemniscal synapses in the VPm by using electrophysiological techniques in combination with pharmacological and/or molecular biological methods.
Figure: Developmetal elimination of leminiscal synapses
Remodeling of the thalamic network after peripheral sensory nerve injury
Somatosensory information is transduced into electric signals at sensory nerve endings. After that, the signals are transmitted via the spinal cord or brain stem nuclei, then the thalamus, and finally led into the somatosensory cortex. If peripheral sensory nerves are injured, various neurochemical/molecular, structural changes are triggered at each level of the somatosensory core, which presumably derive functional alterations such as the change in receptive field of thalamic and cortical neurons. However, synaptic bases underlying such functional remodeling have been unknown. Our studies are now on functional remodeling of the two kinds of glutamatergic and one kind of GABAergic synapses on relay neurons in the somatosensory thalamus after peripheral nerve injury by mainly using electrophysiological techniques.
Figure: Circuit in the primary somatosensory thalamic nuclei (ventrobasal complex)
Research on the molecular mechanism of synaptic transmission in the somatosensory thalamus
A synaptic imbalance of excitatory and inhibitory synaptic inputs contributes to sensory information processing and various neurological disorders, such as epilepsy. However, it is unclear how a synaptic balance of excitatory and inhibitory synaptic inputs is modulated by related molecules. To clarify this molecular mechanism, we explore the involvement of several related molecules (kainate receptors, acetylcholine receptors, and so on) on synaptic transmission in the somatosensory thalamus, using electrophysiological technique.