Neurobiology
Spring 2000
click here for text onlyacronyms
text:
Fundamental Neuroscience
- Zigmond, et al.,:
Read pages 1189-1204 for this lecture
end
NeurobiologySpring 2000click here for text onlyacronyms |
text:
Fundamental Neuroscience - Zigmond, et al.,: Read pages 1189-1204 for this lecture end |
XXXV. Circadian Rhythms back to XXXIV. Lordosis
A. Basic rest-activity cycles about (circa) a day (dian) in length are closely
linked to day-night cycles
1. circadian rhythms exist for virtually every homeostatic system in the body
B. Suprachiasmatic nucleus (SCN: 10,000 neurons in rat; 50,000 in humans) at
the anterior border of the hypothalamus (just above the optic chiasm),
coordinates those rhythms
1. autogenic - spontaneous neural firing in vitro
a. very low resting potentials (near threshold)
b. cyclic firing activity
i. high (8-10 Hz) during the day, low (2-4 Hz) at night
(1) intracellular [Cl-] during the day, ¯ at night
(2) GABA acts as an inhibitory transmitter at night via GABAA
(a) ¯ firing frequency
(i) when [Cl-]i is ¯ GABA induces hyperpolarization
(ii) GABA acts to decrease firing further
(3) GABA acts as an excitatory transmitter during the day
(a) firing frequency
(i) when [Cl-]i is GABA induces depolarization
(ii) positive feedback
ii. clock gene = circadian locomotor output cycles kaput,
on chromosome 5 (Mus)
(1) mammalian clock similar to clock genes in fruit flies & bread mold
(a) all contain PAS domain
(i) PAS-bHLH (basic Helix-loop-Helix) allows protein
to bind to another protein and then to DNA
(ii) photosensitive protein
(b) clock has glutamine rich C-terminal
(i) specific to gene activating proteins
(2) protein product (855 aa) oscillates
(a) regulate its own expression (via PAS-bHLH/glutamine-C)
(i) build up over 24 h ® ¯ clock ® start over
(b) extra copies of clock in genome accelerates cycle
c. cycle can be phase shifted by light, 5-HT, melatonin, VIP/PHI/GRP,
GABA, cAMP, cGMP, partial loss of AVP neurons, stress or B/F
i. rhythms have wave functions
ii. phase is the timing of the peak and slope of the wave
2. endogenous rhythms of the SCN can be visually entrained
a. light can shift the cycle of an organism to coincide with day/night cycles
b. glucose uptake by SCN is significantly greater during daylight
c. fos proto-oncogene (a marker of cell activity =
early-intermediate genes) is differentially transcribed and
translated during daylight
i. immediate-early gene products entrain the pacemaker by
altering DNA transcription
3. a small bundle of fibers from the optic nerve innervates
ventrolateral region of SCN
a. retinohypothalamic tract
i. Glu binds to NMDA receptors in the SCN
(1) NMDA receptors are Ca++ channels
(a) Ca++ activates NOS ® NO ® GC ® cGMP
ii. light entrains circadian rhythms via Glu/NO
(1) light/Glu/NMDA/NO in early evening phase delay the rhythm
(a) in the late night, all advance the rhythm
(b) none have any effect in the day
iii. Glu stimulates neurons which secrete VIP/PHI/GRP (colocalized)
vasoactive intestinal peptide/peptide histidine isoleucine/gastrin-releasing peptide
(1) VIP/PHI/GRP phase advance/delay as does light/Glu/NO
(a) VIP & PHI come from the same pre-promolecule
(2) VIP/PHI/GRP neurons project to SCN GABA interneurons
iv. GABA ® GABAB ¯ Glu release ® ¯ phase delay or advance
(1) most intrinsic SCN neurons are GABAergic
v. VIP/PHI/GRP neurons may also impinge on AVP producing
neurons in dorsomedial SCN
(1) rhythmic function is abolished in AVP-lesioned SCN
(a) restored with AVP-cell transplants
4. optic nerve also projects to the Lateral Geniculate Nucleus of the
thalamus and the superior colliculus or optic tectum (homologs)
a. geniculohypothalamic tract returns information to SCN
i. GABA/NPY neurons
(1) co-release inhibits VIP/PHI/GRP neurons via GABAA
b. LGN also innevates the median/dorsal raphe (d. raphe innervates LGN)
c. median raphe innervates SCN
i. 5-HT7 receptor activity inhibits GABAA effect
(1) GABAB ® 5-HT release in SCN
C. Multiple Oscillators
1. Lateral hypothalamic areas, retrochiasmatic area and ventral hypothalamic
nuclei have weaker rhythmic signals in the absence of SCN
a. SCN is the principal/coordinating center in an extensive system
2. Hypothalamic generation and integration of rhythms are modulated by
AVP, somatostatin (intrinsic to SCN), VIP, enkephalin, substance P
(retinal fibers), NPY, 5-HT...
3. SCN projects to the Habenula and Pineal Gland
a. may have intrinsic rhythms, but clearly driven by SCN
b. pineal produces melatonin from 5-HT during darkness which helps
regulate organismal rhythms
i. melatonin phase-shifts SCN = feedback
ii. may coordinate rhythms longer than 1 day
(1) e.g. estrous/menstrual and circannual reproductive cycles
iii. parietal eye (sharks, frogs, lizards) and photoreceptive pineal (birds)
4. endogenous temperature and sleep/wake cycles can move out of phase
a. SCN affects/regulates/coordinates locomotor, drinking, sleep/wake,
corticosteroid, estrous/ovulation, temperature & melatonin
circadian rhythms
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