The Effects of an Olfactory Bulbectomy on Circadian Rhythm Regulation

Circadian Rhythms are biological patterns which recur in a cycling pattern with a period of approximately 24 hours. All mammals have circadian rhythms which regulate some of their vital bodily functions. This includes their sleep/wake cycle, locomotor activity, food indigestion, drinking behavior, blood temperature, body temperature, hormone secretions, gene expression, etc. The Suprachiasmatic Nucleus (SCN) serves as the chief regulator of circadian rhythms. It is often referred to as the biological clock and is made up of a cluster of circadian oscillating cells which when grouped together produce a highly accurate circadian system. Some cells in the body, in addition to the SCN, are able to maintain circadian rhythmicity but these circadian oscillators rely on the SCN to keep their circadian oscillations. The SCN in a rat is located at the base of the brain, closer to the anterior portion of the brain just above the optic chiasm. The SCN can receive light signals directly from the eye through the retino-hypothalamic tract.

The Olfactory Bulb (OB) has a primary function of regulating the sense of smell, but it also has been shown to keep accurate circadian time independent of the SCN. In previous studies, OB stimulation has been shown to enhance light-induced phase shifts in free-running periods. Its removal has been proven to modify the expression of some circadian behaviors in rodents. For these reasons, we suspect that the olfactory bulb may play some role in circadian rhythm regulation through interaction with the SCN to control expression of circadian behavior.

We hypothesize that Olfactory Bulbectomy (OBx) will have an effect on the SCN’s ability to regulate circadian time and that this will be expressed through a noticeable change in the locomotor activity of our OBx rats.

Experimental Design

In this experiment, we began with 36 three-week old male rats. The rats are lodged in two cage holders where their light schedule can be controlled and their locomotor activity can be recorded. We first exposed the rats to a 5-day light-dark (LD) cycle to synchronize their circadian rhythms to exogenous signals and measure there periods of the rats in a LD cycle. Second, they were placed in a constant dark environment for 7 days. During this time, we observed their endogenous circadian rhythms during a free running period and the rat’s transition from the LD cycle to the DD cycle. After this, we proceeded to perform OBx on our rats. 18 rats received an OBx while the other 18 received a sham lesion. The OBx was followed by a 10 day constant dark period which allows our rats to recover and display any changes in locomotor activity in comparison to before the surgery. Light pulses were given to each rat with an evenly distributed intense light at different times within a 24-hour period. This five minute light pulse is interpreted by the rat as daytime, and the rats will adjust their locomotor activity to this light pulse. We hope to generate a phase response curve (PRC) using our findings. The PRC displays the SCN’s light sensitivity at different times during the day. After the light pulses, the rats will continue on a 10-day constant dark period. During this period of free running, we expect to see a phase shift in the rat’s locomotor activity. Depending on when the light pulse was given, we will see phase delays or phase advances. Following this period, there will be a 10-day LD period. Here, we want to compare the speed of resynchronization of the Sham lesion rats to the OBx rats.

We hope to gain adequate results to verify that the olfactory bulbs do, in fact, have an effect on the SCN’s ability to regulate circadian time.