Distinct roles for GABA across multiple timescales in mammalian circadian timekeeping
Abstract
Each day, over 50 billion synaptic signals, mediated by the neurotransmitter GABA, are sent between neurons in the central circadian pacemaker in the mammalian brain to time and coordinate daily events. Although GABA is the only signaling molecule sent and received by most, if not all of these neurons, its role is not well understood. Past studies have shown paradoxically that GABA can synchronize and desynchronize, as well as excite and inhibit, clock neurons. Through experiments and modeling characterizing the role of GABA in timekeeping, we propose the existence of two types of differentially regulated GABA signaling—fast signaling that regulates neuronal output, and slow signaling that modulates synchrony between neurons—a hypothesis that can explain many previous experimental results.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 30, 2015
- Source ID
- 10.1073/pnas.1420753112
Entities
People
- Daniel B. Forger
- Daniel Dewoskin
- Hugh D. Piggins
- Jihwan Myung
- Mino D C Belle
- Toru Takumi
Organizations
- Air Force Office of Scientific Research
- Biotechnology and Biological Sciences Research Council
- Core Research for Evolutional Science and Technology
- Human Frontier Science Program
- Ministry of Education, Culture, Sports, Science and Technology
- RIKEN
- RIKEN Brain Science Institute
- University of Manchester
- University of Michigan
- Wellcome Trust