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Abstract

Alerting sensory stimuli activate the nucleus Locus Coeruleus (LC) and the associated release of Noradrenaline (NE) improves sensory signaling. We compared the LC-mediated modulation of sensory responses in the primary sensory cortex (S1) and the medial prefrontal cortex (mPFC), a higher integrative cortical region. We performed recordings in S1, mPFC, and LC in response to mild electrical foot shocks (0.5ms, 5mA) and manipulated the activity level of LC-NE system by clonidine, an alpha2-receptor agonist, in the urethane-anesthetized rat. We used systemic and local (in LC) application of clonidine, both leading to decreased level of NE in the brain. 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 injection (50 µl/ml,i.p.) produced a decrease in LC spontaneous firing, however the LC sensory responses were preserved. The short-latency (~17ms) evoked responses in S1 were minimally affected by clonidine, while late response component (~336ms) was decreased. In contrast, bi-directional changes were observed in mPFC. The response amplitude of mPFC neurons was substantially decreased following both local and systemic clonidine administration. Conversely, proportion of initially non-responsive mPFC neurons became responsive following local (22 of neurons) or systemic (38) clonidine application. The LFPs displayed regular slow (~1Hz) oscillations that are characteristic for synchronized cortical state induced by anesthesia. Sensory stimulation evoked transient (~1s) periods of desynchronized (activated) state in 58 of cases, which were abolished by local (60 of cases) and systemic (75) injection of clonidine. The latter effect strongly correlated with a degree of LC inhibition by clonidine. Thus, LC-NE system is critically involved in shifting cortical activity to desynchronized state that is beneficial for sensory processing. Overall, while NE effects were observed in both cortical regions, our results indicate that mPFC receives a stronger NE neuromodulatory input.