The impact of stressors on sensory signal processing regulated by the nucleus locus coeruleus

Stress is an adaptive response to adverse and challenging [behavioral or physiological] circumstances. The neurological cascade of events that follow stressor exposure results in a state of preparedness to respond to bodily demands or environmental challenges. Hypothalamic and extrahypothalamic release of the neuropeptide corticotropin releasing factor (CRF) is important for coordinating the physiological and behavioral responses during stress. A major target for the CRF system is the brainstem nucleus locus coeruleus (LC). The LC is the primary source of norepinephrine (NE) for the entire forebrain and exhibits a range of output that correlate with target NE release. Changes in LC output modulate neuronal responses to salient stimuli, including sensory driven activity within the thalamus. Stress causes a CRF-mediated increase in LC discharge that is dependent upon the nature and intensity of the stress[ors]. However, these effects on downstream target sensory cell physiology remain unclear. To that end, this work examines how different degrees of CRF-mediated LC activation modulate individual neurons responsible for sensory signal processing. The dorsal lateral geniculate nucleus (dLGN) of the thalamus is the primary relay for visual information from the retina to the cortex and is innervated by the LC. Using in vivo extracellular recording in the anesthetized rat, we monitored light-evoked responses from single dLGN neurons before and after CRF-mediated activation of the LC. Exposure to a physiological stressor suppressed dLGN evoked activity, which was blocked in animals pretreated locally with CRF-antagonist. Administration of CRF augmented dLGN neuron sensory evoked responses in an inverted-U dose-response relationship. Together, these data suggest that stressor exposure and subsequent CRF release can alter early stage sensory signal processing via activation of the LC. However, stressor-induced changes in sensory neurons cannot be defined in terms of a singular modulatory effect, but rather exists along a continuum that is dictated by the degree of activation of the CRF-LC-NE pathway. The present findings also suggest a physiological basis for disruption in sensory processing that occurs during intense periods of acute stress or in conjunction with stress disorders associated with dysregulation of the CRF system, e.g. anxiety and post-traumatic stress disorder (PTSD).