Synchronization in the suprachiasmatic nucleus through gap junction and neuromodulator coupling

Abstract

A better understanding in the biological clock is important to help reduce stress on shift workers. Moreover, in the field of medication it will allow for more effective treatments as certain types of medication are more effective when applied at certain moments in the 24-hour cycle. The mammalian biological clock is controlled by a tiny area in the brain called the suprachiasmatic nucleus (SCN). The neurons in the SCN are able to synchronize their clock gene expression to each other through coupling. However, it is unclear how different types of coupling affect the synchronizing property of the SCN. This research explores how two types of coupling, namely gap junction coupling and neuromodulator diffusion shape the synchronous behaviour of a network of SCN neurons. Since data collection in the biological system is challenging, this research is done using a modeling approach. A mathematical single SCN neuron model was used and scaled to a network representation. The individual neuron models were coupled using a gap junction and neuromodulator models. In this research, it was found that gap junction coupling is a precise and strictly local form of coupling. It can synchronize phase errors on the level of action potentials. However in a network there is a maximum number of neurons that can be synchronized, assuming that the number of gap junctions per neuron is limited. Therefore, it was concluded that in large SCN networks gap junction coupling is not able to completely synchronize the network. Neuromodulator coupling is imprecise, slow and global. It can effectively synchronize large phase errors, however, as phase errors become small, neuromodulator coupling loses its synchronizing ability. Therefore, it can only synchronize the daily pattern and cannot synchronize on the level of action potentials. Furthermore, it was shown that neuromodulator diffusion can synchronize SCN networks of arbitrary size.
As a final conclusion, the combination between gap junctions and neuromodulator diffusion is able to synchronize a network completely, perfectly, and rapidly. The neuromodulator component ensures complete synchronization while the gap junctions guarantee perfect synchronization (in the absence of noise). Furthermore, the combination ensures effective synchronization for both small and large phase errors. Therefore, the combination of these two types of coupling is vital in the establishment of network with versatile synchronization properties.