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Abstract:
Noradrenaline (NE) is known to modulate sensory processing by increasing the signal-tonoise
ratio (SNR). Pre- and postsynaptic mechanisms acting on cortical adrenoreceptors have
been implicated. The noradrenergic nucleus Locus Coeruleus (LC) is activated by sensory
stimulation. However, the contribution of the sensory-evoked discharge in LC to modulation
of cortical sensory responses is not well understood. We compared the effects of systemic
or local (in LC) application of clonidine, an alpha2-receptor agonist, which is known to
inhibit LC-NE neurons, on sensory responses in two cortical targets of LC. Simultaneous
recordings in LC, primary Somatosensory (S1) and medial Prefrontal Cortex (mPFC) were
performed in the urethane-anesthetized rat. Electrical foot shocks (FS) of the contralateral
hind paw served as somatosensory stimuli (0.5ms, 5mA). The LC responses to FS differed
dramatically after local and systemic clonidine administration. Iontophoretic application of
clonidine (50nA, 50μl/ml, 20min) into LC resulted in complete cessation of both spontaneous
and evoked activity of LC-NE neurons. Systemic clonidine (50 μl/ml, i.p.) produced a decrease
in LC firing (less than 50 baseline for 30 min), however the LC responses to FS were
preserved. Both local and systemic clonidine administration increased spontaneous activity
in S1 and mPFC. The evoked responses in S1 were unchanged under condition of complete
inhibition of the ipsilateral LC by local application of clonidine (n=13) and decreased during
systemic clonidine condition (n=13). In mPFC, 8 units (40) increased and 9 units (45)
decreased the response amplitude following local inhibition of LC. Four out of 24 mPFC
neurons showed increased responses after systemic clonidine injection. Strikingly, 20 of
initially non-responsive mPFC neurons became responsive (n=7) in case of local inhibition of
LC. The same phenomenon was observed during systemic clonidine in 58 of cases (n=14).
Thus, blocking the LC sensory-evoked discharge differentially affected signal processing in
S1 and mPFC. The responses in S1 were preserved, while responses of a large proportion of
mPFC neurons ( 50) were affected. We observed the opposite effects in S1 (decrease SNR)
and mPFC (increased signaling) after activation of the alpha2 receptors in the entire brain.
Overall, we conclude that alpha2 receptors are involved in sensory signal processing in both
cortical regions, but mPFC receives a stronger NE neuromodulatory input.