Biology Reference
In-Depth Information
Rose, Epperson, Carey, & Martin, 2007
), where it is produced. A key
enzyme in the synthesis pathway of BHB, hydroxymethylglutaryl-CoA
synthase 2 (HMGCS2), is also upregulated in the liver during hibernation
(
Epperson, Dahl, & Martin, 2004
).
Seasonal molecular changes also occur in the brain to facilitate this met-
abolic fuel switch. Monocarboxylic acid transporter 1 (MCT1), also known
as solute carrier family 16, member 1 (SLC16A1), is a ketone transporter that
facilitates transport of BHB into the brain. This transporter is upregulated at
the blood-brain barrier during torpor in ground squirrels (
Andrews et al.,
2009
).
SLC16A1
mRNA levels are also upregulated in the cerebral cortex
and hypothalamus during hibernation (
Schwartz et al., 2013
).
4.3. Central nervous system in hibernation
Like the heart, one area of the brain, the hypothalamus, remains active
throughout the hibernation season (
Bratincsak et al., 2007; Kilduff,
Miller, Radeke, Sharp, &Heller, 1990; Kilduff, Sharp, &Heller, 1982
). This
region of the brain is involved in many aspects important for hibernation and
hibernation preparation, including food intake, circadian rhythms, sleep,
and thermoregulation. The SCN of the hypothalamus, containing the cir-
cadian clock, is a likely candidate for the control of circannual hibernation
timing.
c-fos
mRNA, used as a marker for neuronal activation, increases in
the SCN during torpor and peaks during arousal (
Bitting et al., 1994;
Bratincsak et al., 2007
), suggesting that it is involved in torpor bout timing.
Broad hypothalamic lesions prevented successful hibernation (
Satinoff,
1967
) and focused lesions specific to the SCN altered hibernation timing
in ground squirrels (
Ruby, Dark, Heller, & Zucker, 1996
), which suggests
that the hypothalamus is important for both hibernation induction and
maintenance. However, clock gene rhythms (
per1
,
per2
,
bmal1
) are suppres-
sed during hibernation (
Revel et al., 2007
), so it is unclear how or if the
circadian clock is specifically involved in hibernation timing.
In contrast to the hypothalamus, the rest of the brain is relatively quiescent
during hibernation. The cerebral cortex is the first area of the brain to lose
activity as the animal goes into a torpor bout, followed by the brainstem
and reticular formation, thalamus, and limbic system (
Heller, 1979
). They
regain activity upon arousal in the opposite order. The cerebral cortex, hip-
pocampus, and thalamus all exhibit extensive neurite and synaptic plasticity
during hibernation, with synapses dissociating during torpor but reconnecting
appropriately upon arousal to an IBA (
Magari˜os et al., 2006; Popov et al.,
