Bn. Smith et al., Serotonergic modulation of retinal input to the mouse suprachiasmatic nucleus mediated by 5-HT1B and 5-HT7 receptors, J BIOL RHYT, 16(1), 2001, pp. 25-38
Serotonin (5-HT) and 5-HT receptor agonists can modify the response of the
mammalian suprachiasmatic nucleus (SCN) to light. It remains uncertain whic
h 5-HT receptor subtypes mediate these effects. The effects of 5-HT recepto
r activation on optic nerve-mediated input to SCN neurons were examined usi
ng whole-cell patch-clamp recordings in horizontal slices of ventral hypoth
alamus from the male mouse. The hypothesis that 5-HT reduces the effect of
retinohypothalamic tract (RHT) input to the SCN by acting at 5-HT1B recepto
rs was tested first. As previously described in the hamster, a mixed 5-HT1A
/1B receptor agonist, 1-[3-(trifluoromethyl)phenyl] -piperazine hydrochlori
de (TFMPP), reduced the amplitude of glutamatergic excitatory postsynaptic
currents (EPSCs) evoked by selectively stimulating the optic nerve of wild-
type mice. The agonist was negligibly effective in a. 5-HT1B receptor knock
out mouse, suggesting minimal contribution of 5-HT1A receptors to the TFMPP
-induced reduction in the amplitude of the optic nerve-evoked EPSC. We next
tested the hypothesis that 5-HT also reduces RHT input to the SCN via acti
vation of 5-HT7 receptors, The mixed 5-HT1A/7 receptor agonist, R(+)-8-hydr
oxy-2-(di-n-propylamino) tetralin hydrobromide (8-OH-DPAT), reduced the evo
ked EPSC amplitude in both wild-type and 5-HT1B receptor knockout mice. Thi
s effect of 8-OH-DPAT was minimally attenuated by the selective 5-HT1A rece
ptor antagonist WAY 100635 but was reversibly and significantly reduced in
the presence of ritanserin, a mixed 5-HT2/7 receptor antagonist. Taken toge
ther with the authors' previous ultrastructural studies of 5-HT1B receptors
in the mouse SCN, these results indicate that in the mouse, 5-HT reduces R
HT input to the SCN by acting at 5-HT1B receptors located on RHT terminals.
Moreover, activation of 5-HT7 receptors in the mouse SCN, but not 5-HT1A r
eceptors, also results in a reduction in the amplitude of the optic nerve-e
voked EPSC. The findings indicate that 5-HT may modulate RHT glutamatergic
input to the SCN through 2 or more 5-HT receptors. The likely mechanism of
altered RHT glutamatergic input to SCN neurons is an alteration of photic e
ffects on the SCN circadian oscillator.