Corticotropin-Releasing Factor Acting at the Locus Coeruleus Disrupts Thalamic and Cortical Sensory-Evoked Responses

Abstract

Stress and stress-related psychiatric disorders, including post-traumatic stress disorder, are associated with disruptions in sensory information processing. The neuropeptide, corticotropin-releasing factor (CRF), coordinates the physiological and behavioral responses to stress, in part, by activating the locus coeruleus-norepinephrine (LC-NE) projection system. Although the LC-NE system is an important modulator of sensory information processing, to date, the consequences of CRF activation of this system on sensory signal processing are poorly understood. The current study examined the dose-dependent actions of CRF at the LC on spontaneous and sensory-evoked discharge of neurons within the thalamus and cortex of the vibrissa somatosensory system in the awake, freely moving rat. Peri-LC infusions of CRF resulted in a dose-dependent suppression of sensory-evoked discharge in ventral posterior medial thalamic and barrel field cortical neurons. A concurrent increase in spontaneous activity was observed. This latter action is generally not found with iontophoretic application of NE to target neurons or stimulation of the LC-NE pathway. Net decreases in signal-to-noise of sensory-evoked responses within both regions suggest that under conditions associated with CRF release at the LC, including stress, the transfer of afferent information within sensory systems is impaired. Acutely, a suppression of certain types of sensory information may represent an adaptive response to an immediate unexpected stressor. Persistence of such effects could contribute to abnormalities of information processing seen in sensorimotor gating associated with stress and stress-related psychopathology.

Ultrastructural evidence for synaptic contacts between cortical noradrenergic afferents and endocannabinoid-synthesizing post-synaptic neurons

“…The release of NE is related to arousal states and this in turn has profound effects on cognitive, executive and behavioral processes (Lapiz and Morilak, 2006; Arnsten, 2007). Considering that NE is a key regulator of FC function, either too little or too much adrenergic neurotransmission results in suboptimal neuronal responses to exteroceptive or interoceptive stimuli (Berridge and Waterhouse, 2003; Devilbiss et al, 2012). High levels of noradrenergic transmission are implicated in behavioral, cognitive, emotional and physiological manifestations characteristic of depression and anxiety (Miller et al, 1996; Sands et al, 2000; Cottingham and Wang, 2012).…”

The impact of hemodynamic stress on sensory signal processing in the rodent lateral geniculate nucleus

“…persistent CRF-induced elevation of tonic LC output. More recently however, Devilbiss et al (2012) showed that intra-LC administration of CRF (300 ng) suppressed sensory evoked responses among ventral posteromedial (VPM) thalamic neurons 0–30 min post-CRF. These results are consistent with those found in the current study, i.e.…”

The role of the dynorphin/κ opioid receptor system in anxiety

“…Dynorphin and κ opioid receptors are coexpressed within the LC on noradrenergic (NA) neurons [67,[82][83][84][85] . Previous reports have shown that both stress and CRF engage in LC NA cell firing [86,87] . Ai-Hasani et al (2013) first reported that κ opioid receptors within the LC NA nuclei modulate the reinstatement of cocaine place preference through a noradrenergic mechanism [88] .…”