Understanding how information is encoded in the nervous system is essential to understanding how animal behavior is generated. However, few model systems have well-characterized neural correlates that directly correspond to specific behavioral outputs. One exception is the generation of innate circadian rhythmicity. Daily behavioral rhythms (~ 24 hrs) are a universal trait of animals, vital for adaptation to the environment and overall fitness. In mammals, the principal circadian clock is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. To understand how circadian time is encoded in the SCN and translated into circadian behavioral outputs, this project investigates how the daily pattern of neuronal activity in regulated. Using transgenic manipulation of ion channel expression and function, the consequences of fundamentally altering the daily rhythm of neural activity in the SCN will be investigated by electrophysiology and behavioral studies. Alteration of ion channel activity is predicted to change the expression of circadian behaviors. This project is expected to advance knowledge in how the brain controls innate circadian behavior, but more broadly, provides a novel approach for understanding the direct links between neural coding and the resultant behavioral effects.
Students involved in this research will learn an integrative approach to biological function, from molecular-cell-circuit-system/behavior. In particular, training in electrophysiology, a discipline traditionally without adequate representation of women and minorities, is the cornerstone of the research project. The lab draws upon the inner-city Baltimore area both for student involvement and dissemination of major findings through local public outlets such as the Baltimore Sun newspaper and Maryland Science Center.
Circadian Rhythm as a Model for Neural Coding Innate behaviors in organisms arise from the integration of neural information at the cellular, circuit, and system levels. One of the goals in the field of neuroscience is to understand how information flows through these levels to generate a stereotypical behavior. Few behaviors have well-characterized neural correlates at each level; however, one exception is the generation of innate circadian rhythmicity. Daily (24-hour, circadian) behavioral rhythms are a universal trait of living organisms, vital for adaptation to the environment and overall fitness. In mammals, the principal circadian pacemaker is the suprachiasmatic nucleus (SCN) of the hypothalamus. The neurons of the SCN circuit exhibit circadian patterning of neural activity that instructs the circadian behavior of the whole animal. Our project sought to understand how the circadian pattern of neural activity is produced in the SCN, and what the consequences of altering the neural activity are on circadian behavior. We manipulated the expression of proteins in the SCN called ion channels. Ion channels generate the ionic currents that underlie the characteristic electrical signals used by neurons to encode information. We used genetic manipulation of ion channel expression and function to generate a transgenic mouse, where the consequences of altering the daily rhythm of neural activity in the SCN could be investigated with electrophysiological and behavioral studies. We found that one type of potassium current, which is expressed at night, plays a prominent role in shaping neural activity in the SCN circuit. Altering the expression of this ion channel profoundly affects neural activity in the SCN circuit, but this alteration has a surprisingly limited impact on circadian behavior. These results reveal that the majority of the SCN circuit is dispensable for normal circadian rhythmicity, but plays an important role in buffering the intrinsic circadian clock from environmental perturbation. The results of this study are relevant for understanding how neurons encode information and drive behaviors, as well as for revealing new ways of treating jet lag, sleep and attention disorders, and other disorders involving alterations of daily physiological function. Trainees involved in this research learned an integrative approach to biological function, from molecular-cell-circuit-system to behavior. In particular, training in electrophysiology for women and underrepresented minorities was a central goal of the research project. Major findings were disseminated through open access scientific publications and local public media outlets such as the Baltimore Sun newspaper and The Maryland Science Center.
