A group of researchers led by Associate Professor KIMURA Fumitaka at the Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, clarified that multiple mechanisms were involved in the formation of neuronal circuits in the cerebral cortex. This group also clarified that a substance similar to cannabinoid, an active substance of cannabis, played an important role in the formation of neuronal circuits, and that the intake of cannabis pruned even necessary synapses, destroying neuronal circuits, a world first.
It was known that neural activities by presynaptic and postsynaptic cells greatly affected the formation of neural circuits, but the kinds of neural activities involved were not clear. Neutral activities in thalamocortical projections to the cortex are complicated, proceeding in two steps. As the cerebral cortex grows, unnecessary projections are pruned, eventually forming correct projections. However, this mechanism was unclear.
This group had discovered that other areas of the cerebral cortex had a rule called spike timing-dependent plasticity (STDP), that is, the synaptic strength was determined in order of firing of presynaptic and postsynaptic cells, and that this rule suddenly changed in one process during circuit formation. For this reason, this group focused on the possibility that the rule would suddenly change at thalamocortical synapses as they performed their research.
Suppression of thalamocortical projection by chronic administration of D9-THC (cannabinoid, active ingredient of marijuana). Photomicrograph of cerebral cortex from transgenic mice having GFP in thalamocortical axons at postnatal day 7 (P7). Normal thalamocortical projection. In the middle layer (layer 4), blobs of GFP showing dense termination of thalamocortical axons can be seen (under number 1~5). (bottom): Thalamocortical projection from a mouse received chronic administration of D9-THC (P2~7) at P7. Massive retraction of thalamocortical projection including middle layer (layer 4) can be observed. Neurosciencenews image is credited to the researchers.
As a result, when thalamocortical projections were formed, first, synaptic connections were strengthened due to activities in presynaptic and postsynaptic cells, and projections extended over wide areas, but following that, the rule changed so that the synchronized activities weakened the synaptic connections, and extra projections were pruned. In addition, it was found that at the time of weakening of synaptic connections, cannabinoid was released from neural cells via synchronized activities, thereby retracting unnecessary neuron projections. Research showed that neuron projections retracted when cannabinoid was externally taken as well. Furthermore, it was also found that projections remained disorderly in cannabinoid receptors (CB1Rs) knock-out mice.
This group’s achievement clarified scientific grounds that cannabis and intoxicating drugs had adverse effects on the brain. By disabling the functions of cannabinoid, it may be possible to suppress the breakdown of neural circuits. It is expected that this group’s achievement will be used for recovering functions impaired by brain damage and dementia.
September 12, 2016
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