The Effects of Tonic Locus Ceruleus Output on Sensory-Evoked Responses of Ventral Posterior Medial Thalamic and Barrel Field Cortical Neurons in the Awake Rat

Abstract

In mammals, the pontine nucleus locus ceruleus (LC) is the sole source of norepinephrine (NE) projections to the forebrain. Increasing tonic discharge of LC neurons elevates extracellular levels of NE in the cortex and thalamus. Tonic LC discharge is linked to the level of wakefulness and behavioral performance, demonstrating an optimal firing rate during sustained attention tasks. Iontophoretic application of NE to target neurons in the forebrain has been shown to produce a diverse set of neuromodulatory actions, including augmentation of synaptically evoked discharge as well as suppression of spontaneous and stimulus-evoked firing patterns. Iontophoretic studies cataloged potential NE effects; however, the context in which such actions could occur in awake behaving animals remained controversial. To address this issue, the current study examined the effects of increasing tonic LC output on spontaneous and stimulus-evoked discharge of neurons within the ventroposterior medial (VPM) thalamus and barrel field (BF) somatosensory cortex of awake animals using multichannel extracellular recording strategies. The present findings indicate two primary outcomes that result from increasing frequencies of LC stimulation, either an inverted-U facilitating response profile or monotonic suppression of sensory-evoked neuronal responses. Increased tonic LC output generally decreased neuronal response latency measures for both BF cortical and VPM thalamic cells. LC-mediated effects on target VPM and BF cortical neuron sensory processing are consistent with previous demonstrations of NE modulatory actions on central neurons but indicate that such actions are cell specific. Moreover, clear differences were observed between the modulation of VPM and BF cortical cells. These data suggest that sensory signal processing is continually altered over the range of tonic LC discharge frequencies that occur in the waking animal. Such changes may account for LC-mediated shifts in sensory network performance across multiple stages of arousal and attention.

Trial-to-trial variability in the responses of neurons carries information about stimulus location in the rat whisker thalamus

“…On the one hand, these anesthetized conditions are convenient to maintain the animal brain in a reasonably stable state throughout long stimulation protocols (48). On the other hand, however, thalamic responses are highly dependent on the arousal and behavioral state of the animal (48)(49)(50)(51). Inferences about sensory processing based on anesthetized data should therefore be cautious: Our experimental conditions simply represent a model to gain general insights about the possible computational roles of trial-to-trial variability in neural responses from a rate-coding perspective.…”

Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states

“…By contrast, BF lesion reduces whiskerevoked activity in the barrel cortex [150]. LC stimulation enhances cortical activity [99,[151][152][153] and the responses of cortical neurons to sensory stimulation [154], and NA directly modulates cortical neuronal network dynamics [155,156]. For instance, during locomotion, NA leads to enhanced activity in both PV and SOM-containing interneurons in the visual cortex [157] and may also act on astrocytes to prime the neuronal network [158].…”

Context-dependent Dynamic Processes in Attention Deficit/Hyperactivity Disorder: Differentiating Common and Unique Effects of State Regulation Deficits and Delay Aversion

“…The LC system, located in the brainstem, has also been related to arousal/state regulation processes. Tonic activity seems to be associated with the regulation of arousal and a variety of state-dependent processes, such as sensory information processing, attention, working memory, and motor processes (Devilbiss and Waterhouse, 2004;Arnsten and Dudley, 2005).…”