The Laboratory of Braintime
Neural Circuit of Circadian Clocks
While a single cell is fully capable of maintaining a circadian clock, evolution chose a multi-cellular clock system in mammals. We have previously found that the main circadian clock, the suprachiasmatic nucleus (SCN), can be reduced to a simple neural circuit of two oscillators. The two-oscillator model predicts novel stability pockets that enable previously unforeseen circadian behaviors. These new insights provide us with specific model-based strategies that we can test in vivo and ex vivo. We seek clinical applications of these findings to quickly stabilize circadian rhythms under unusual seasonal conditions or after abrupt transitions to a new day-night cycle.
Circadian Regulation of Time Perception and Mood
The seasonality is an important cue for mood fluctuation, as evidenced by a seasonal peak of suicide rate among the major depression and affective disorder patients (let us recite T.S. Eliot’s "April is the cruellest month"). Molecular studies from post-mortem samples show clear correlation between depression and temporally disrupted expression of circadian genes. Since the seasonal rhythm of our body is sustained by the circadian clock, there must exist a physiological connection between the depressive mood state and molecular circadian rhythms. Psychological studies show that the second-to-minute scale timeperception (subjective evaluation of time duration) can be a good indicator of the mood state, and classical studies in chronobiology demonstrated connection between circadian rhythms and time perception. There is strong evidence that the perceived time length is a function of dopamine and serotonin release. Incidentally, enzymes involved with synthesis and metabolism of the two neurotransmitters are regulated circadianly. We are putting these clues together to understand how circadian rhythms modulate degrees of time perception and distinct mood states. These studies have substantial potential to open up new avenues of treatment for abnormal mood conditions.
Natural Philosophy of Subjective Time
Time has occupied a special place in the thoughts of neuroscientists and philosophers alike. Building on Aristotle’s concept of the now, or the nun, Henri Bergson notes that conscious awareness is intermingled with duration in time, or durée. Linear, quantifiable time is only possible when it can be projected onto space, but this cannot be done with the time of consciousness. The concept of linear time has not always been universal. In many ancient cultures, time is cyclic, since the success of agriculture depends on the correct prediction of the seasonal cycle. The repeating rhythms of the year, and of its daily subdivisions, are the fundamental features of life, known as biological rhythms. Neuroscience reveals that these rhythms are entangled with perceptual timescales of seconds to minutes, which closely relates to mood and is integral to conscious experience. The entanglement of subjective awareness and time is an important concept in cognitive neuroscience under the term episodic memory, which Endel Tulving illustrates as “the brain’s time machine”. Our memory of a particular subjective experience cannot be retrieved unless a point in time is specified, which is itself associated with a qualitative context. Thebrain’s hippocampus is thought to be a “Google” for episodic memory, and search by spatial context is possible because it contains “place cells” that identify where a person is located in an environment. It has only recently become known that the hippocampus also houses “time cells” that make place and time inseparable components of episodic memory. These new findings in neuroscience shed new light on subjective time and have the potential to “naturalize” epistemology, although perhaps not in the way W.V.O. Quine had originally envisioned. Understanding time in the brain therefore has a great potential to reveal the secrets of the human mind.