Circadian Rhythms

Circadian Rhythms: keeping time, from molecules to behavior

The circadian molecular oscillator

Circadian rhythms are ~24‑hour cycles in physiology and behavior that let organisms anticipate daily environmental changes. A conserved transcription‑translation feedback loop underlies these rhythms, but post‑transcriptional regulation (alternative splicing, RNA stability, translation control) is now recognized as also crucial.

Core molecular clock – in Drosophila, CLOCK (CLK) and CYCLE (CYC) drive rhythmic transcription of period (per) and timeless (tim); PER/TIM proteins feed back to repress CLK/CYC, closing the loop.
RNA‑level fine‑tuning – miRNAs, RNA‑binding proteins and splice factors shape clock mRNA abundance and isoform choice, buffering noise and enabling environmental adaptation. For example, tight 3′‑UTR control of Clk“denoises” rhythms, ensuring each individual fly maintains a robust behavioral period.
Temperature and light entrainment – beyond transcriptional effects, the clock senses ambient temperature and photoperiod through RNA processing events that adjust protein isoforms and translation rates.

The neuronal circadian network

1. An anatomically distributed but functionally coupled pacemaker

Architecture. Drosophila’s circadian circuit comprises six neuronal classes: small & large ventro‑lateral (s‑LNvs, l‑LNvs), dorso‑lateral (LNds) and three dorsal groups (DN1‑DN3), plus lateral‑posterior neurons (LPNs). Each harbours its own TTFL yet they communicate through neuropeptides and fast neurotransmitters.
Key transmitter – PDF. Pigment‑Dispersing Factor, released exclusively from LNvs, synchronises the network and sustains locomotor rhythms in constant darkness. Loss of pdf or its receptor abolishes coherence, proving that timing is a circuit‑level trait rather than a mere sum of cell‑autonomous clocks.

2. How neuronal coupling shapes daily behavior

Morning vs Evening oscillators. Temperature, photoperiod, and PDF tone shift phase relationships among LNvs (morning) and LNds/DNs (evening), adjusting the fly’s activity peaks to season and latitude.
Circuit plasticity. PDF strengthens molecular rhythms in downstream neurons yet simultaneously dampens its own transcription (negative auto‑regulation), providing a self‑limiting mechanism that avoids hyper‑synchrony.