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Abstract

Noradrenaline (NE) is known to modulate sensory processing by increasing the signal-to-noise 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 sensoryevoked
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 blocking 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.