scholarly journals Phasic locus coeruleus activity regulates cortical encoding of salience information

2018 ◽  
Vol 115 (40) ◽  
pp. E9439-E9448 ◽  
Author(s):  
Elena M. Vazey ◽  
David E. Moorman ◽  
Gary Aston-Jones

Phasic activation of locus coeruleus (LC)-norepinephrine (NE) neurons is associated with focused attention and behavioral responses to salient stimuli. We used cell-type–specific optogenetics and single-unit neurophysiology to identify how LC activity influences neural encoding of sensory information. We found that phasic, but not tonic, LC-NE photoactivation generated a distinct event-related potential (ERP) across cortical regions. Salient sensory stimuli (which innately trigger phasic LC activity) produced strong excitatory cortical responses during this ERP window. Application of weaker, nonsalient stimuli produced limited responses, but these responses were elevated to salient stimulus levels when they were temporally locked with phasic LC photoactivation. These results demonstrate that phasic LC activity enhances cortical encoding of salient stimuli by facilitating long-latency signals within target regions in response to stimulus intensity/salience. The LC-driven salience signal identified here provides a measure of phasic LC activity that can be used to investigate the LC’s role in attentional processing across species.

2015 ◽  
Vol 112 (41) ◽  
pp. 12834-12839 ◽  
Author(s):  
Houman Safaai ◽  
Ricardo Neves ◽  
Oxana Eschenko ◽  
Nikos K. Logothetis ◽  
Stefano Panzeri

Neuronal responses to sensory stimuli are not only driven by feedforward sensory pathways but also depend upon intrinsic factors (collectively known as the network state) that include ongoing spontaneous activity and neuromodulation. To understand how these factors together regulate cortical dynamics, we recorded simultaneously spontaneous and somatosensory-evoked multiunit activity from primary somatosensory cortex and from the locus coeruleus (LC) (the neuromodulatory nucleus releasing norepinephrine) in urethane-anesthetized rats. We found that bursts of ipsilateral-LC firing preceded by few tens of milliseconds increases of cortical excitability, and that the 1- to 10-Hz rhythmicity of LC discharge appeared to increase the power of delta-band (1–4 Hz) cortical synchronization. To investigate quantitatively how LC firing might causally influence spontaneous and stimulus-driven cortical dynamics, we then constructed and fitted to these data a model describing the dynamical interaction of stimulus drive, ongoing synchronized cortical activity, and noradrenergic neuromodulation. The model proposes a coupling between LC and cortex that can amplify delta-range cortical fluctuations, and shows how suitably timed phasic LC bursts can lead to enhanced cortical responses to weaker stimuli and increased temporal precision of cortical stimulus-evoked responses. Thus, the temporal structure of noradrenergic modulation may selectively and dynamically enhance or attenuate cortical responses to stimuli. Finally, using the model prediction of single-trial cortical stimulus-evoked responses to discount single-trial state-dependent variability increased by ∼70% the sensory information extracted from cortical responses. This suggests that downstream circuits may extract information more effectively after estimating the state of the circuit transmitting the sensory message.


2011 ◽  
Vol 105 (1) ◽  
pp. 69-87 ◽  
Author(s):  
David M. Devilbiss ◽  
Barry D. Waterhouse

Neurons of the nucleus locus coeruleus (LC) discharge with phasic bursts of activity superimposed on highly regular tonic discharge rates. Phasic bursts are elicited by bottom-up input mechanisms involving novel/salient sensory stimuli and top-down decision making processes; whereas tonic rates largely fluctuate according to arousal levels and behavioral states. Although it is generally believed that these two modes of activity differentially modulate information processing in LC targets, the unique role of phasic versus tonic LC output on signal processing in cells, circuits, and neural networks of waking animals is not well understood. In the current study, simultaneous recordings of individual neurons within ventral posterior medial thalamus and barrel field cortex of conscious rats provided evidence that each mode of LC output produces a unique modulatory impact on single neuron responsiveness to sensory-driven synaptic input and representations of sensory information across ensembles of simultaneously recorded cells. Each mode of LC activation specifically modulated the relationship between sensory-stimulus intensity and the subsequent responses of individual neurons and neural ensembles. Overall these results indicate that phasic versus tonic modes of LC discharge exert fundamentally different modulatory effects on target neuronal circuits within the rodent trigeminal somatosensory system. As such, each mode of LC output may differentially influence signal processing as a means of optimizing behaviorally relevant neural computations within this sensory network. Likely the ability of the LC system to differentially regulate neural responses and local circuit operations according to behavioral demands extends to other brain regions including those involved in higher cognitive functions.


2021 ◽  
Author(s):  
Joseph T Francis ◽  
Anna Rozenboym ◽  
Lee von Kraus ◽  
Shaohua Xu ◽  
Pratik Chhatbar ◽  
...  

Lost sensations, such as touch, could be restored by microstimulation (MiSt) along the sensory neural substrate. Such neuroprosthetic sensory information can be used as feedback from an invasive brain-machine interface (BMI) to control a robotic arm/hand, such that tactile and proprioceptive feedback from the sensorized robotic arm/hand is directly given to the BMI user. Microstimulation in the human somatosensory thalamus (Vc) has been shown to produce somatosensory perceptions. However, until recently, systematic methods for using thalamic stimulation to evoke naturalistic touch perceptions were lacking. We have recently presented rigorous methods for determining a mapping between ventral posterior lateral thalamus (VPL) MiSt, and neural responses in the somatosensory cortex (S1), in a rodent model (Choi et al., 2016; Choi and Francis, 2018). Our technique minimizes the difference between S1 neural responses induced by natural sensory stimuli and those generated via VPL MiSt. Our goal is to develop systems that know what MiSt will produce a given neural response and possibly a more natural "sensation." To date, our optimization has been conducted in the rodent model and simulations. Here we present data from simple non-optimized thalamic MiSt during peri-operative experiments, where we MiSt in the VPL of macaques with a somatosensory system more like humans. We implanted arrays of microelectrodes across the hand area of the macaque S1 cortex as well as in the VPL thalamus. Multi and single-unit recordings were used to compare cortical responses to natural touch and thalamic MiSt in the anesthetized state. Post stimulus time histograms were highly correlated between the VPL MiSt and natural touch modalities, adding support to the use of VPL MiSt towards producing a somatosensory neuroprosthesis in humans.


2003 ◽  
Vol 89 (3) ◽  
pp. 1205-1213 ◽  
Author(s):  
Marcello Massimini ◽  
Mario Rosanova ◽  
Maurizio Mariotti

Intracellular studies reveal that, during slow wave sleep (SWS), the entire cortical network can swing rhythmically between extremely different microstates, ranging from wakefulness-like network activation to functional disconnection in the space of a few hundred milliseconds. This alternation of states also involves the thalamic neurons and is reflected in the EEG by a slow (<1 Hz) oscillation. These rhythmic changes, occurring in the thalamo-cortical circuits during SWS, may have relevant, phasic effects on the transmission and processing of sensory information. However, brain reactivity to sensory stimuli, during SWS, has traditionally been studied by means of sequential averaging, a procedure that necessarily masks any short-term fluctuation of responsiveness. The aim of this study was to provide a dynamic evaluation of brain reactivity to sensory stimuli in naturally sleeping humans. To this aim, single-trial somatosensory evoked potentials (SEPs) were grouped and averaged as a function of the phase of the ongoing sleep slow (<1 Hz) oscillation. This procedure revealed a dynamic profile of responsiveness, which was conditioned by the phase of the spontaneous sleep EEG. Overall, the amplitude of the evoked potential changed sistematically, increasing and approaching wakefulness levels along the negative slope of the EEG oscillation and decaying below SWS average levels along the positive drift. These marked and fast changes of stimulus-correlated electrical activity involved both short (N20) and long latency (P60 and P100) components of SEPs. In addition, the observed short-term response variability appeared to be centrally generated and specifically related to the evolution of the spontaneous oscillatory pattern. The present findings demonstrate that thalamo-cortical processing of sensory information is not stationary in the very short period (approximately 500 ms) during natural SWS.


2020 ◽  
Author(s):  
Sergio Osorio ◽  
Martín Irani ◽  
Javiera Herrada ◽  
Francisco Aboitiz

AbstractThe ability to detect novelty in sensory stimuli is at the base of autonomic and goal-directed behavior. Pupil size, a proxy of the Locus Coeruleus-Norepinephrine system, is sensitive to auditory novelty. However, whether this response reliably reflects conscious processing of novelty remains contentious. Here, we characterized pupil and electrophysiological responses during conscious and subconscious processing of auditory novelty by presenting participants deviant stimuli that were below and above their discriminatory thresholds. We found higher pupil responses to subthreshold targets that were not consciously perceived as deviant stimuli. Larger pupil size and dilation rates were associated to more negative Event-Related Potential values extracted from temporal, prefrontal and anterior cingulate regions. We suggest that increased phasic responses to deviant targets that escape conscious perception reflect Norepinephrine-mediated adaptation of arousal levels in order to meet the perceptual and behavioral demands imposed by the task at hand.


2021 ◽  
Author(s):  
Mehdi Sicre ◽  
Julie Meffre ◽  
Frederic Ambroggi

ABSTRACTThe thalamus is a phylogenetically well-preserved structure. Known to densely contact cortical regions, its role in the transmission of sensory information to the striatal complex has been widely reconsidered in recent years. The parafascicular of the thalamus (Pf) has been implicated the orientation of attention towards salient sensory stimuli. In a stimulus-driven reward seeking task, we sought to characterize the electrophysiological activity of Pf neurons in rats. We observed a predominance of excitatory responses over inhibitory responses for all events of the task. Neurons responded more strongly to the stimulus compared to lever-pressing and collecting reward, confirming the strong involvement of the Pf in sensory information processing. The use of long sessions allowed us to compare neuronal responses to stimuli when the animal engaged in action or when it did not. We distinguished two populations of neurons responding in an opposite way: MOTIV+ neurons responded more intensively to stimuli followed by a behavioral response than those that did not. Conversely, MOTIV-neurons responded more strongly when the stimulus was ignored by the animal. In addition, MOTIV-neurons excitations appeared at a shorter latency after the stimulus than MOTIV+ neurons. Through this encoding, Pf could perform an early selection of environmental stimuli transmitted to the striatum according to motivational level.HIGHLIGHTSPf neurons respond to reward-predicting stimuli and reward-related actionsMOTIV+ Pf neurons were more active to stimuli evoking reward-seekingMOTIV- Pf neurons were more active to stimuli ignored by the animalStimuli-evoked excitations latencies were shorter in MOTIV- than MOTIV+ neurons


2021 ◽  
Vol 11 (7) ◽  
pp. 835
Author(s):  
Alexander Rokos ◽  
Richard Mah ◽  
Rober Boshra ◽  
Amabilis Harrison ◽  
Tsee Leng Choy ◽  
...  

A consistent limitation when designing event-related potential paradigms and interpreting results is a lack of consideration of the multivariate factors that affect their elicitation and detection in behaviorally unresponsive individuals. This paper provides a retrospective commentary on three factors that influence the presence and morphology of long-latency event-related potentials—the P3b and N400. We analyze event-related potentials derived from electroencephalographic (EEG) data collected from small groups of healthy youth and healthy elderly to illustrate the effect of paradigm strength and subject age; we analyze ERPs collected from an individual with severe traumatic brain injury to illustrate the effect of stimulus presentation speed. Based on these critical factors, we support that: (1) the strongest paradigms should be used to elicit event-related potentials in unresponsive populations; (2) interpretation of event-related potential results should account for participant age; and (3) speed of stimulus presentation should be slower in unresponsive individuals. The application of these practices when eliciting and recording event-related potentials in unresponsive individuals will help to minimize result interpretation ambiguity, increase confidence in conclusions, and advance the understanding of the relationship between long-latency event-related potentials and states of consciousness.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Emily T. Wood ◽  
Kaitlin K. Cummings ◽  
Jiwon Jung ◽  
Genevieve Patterson ◽  
Nana Okada ◽  
...  

AbstractSensory over-responsivity (SOR), extreme sensitivity to or avoidance of sensory stimuli (e.g., scratchy fabrics, loud sounds), is a highly prevalent and impairing feature of neurodevelopmental disorders such as autism spectrum disorders (ASD), anxiety, and ADHD. Previous studies have found overactive brain responses and reduced modulation of thalamocortical connectivity in response to mildly aversive sensory stimulation in ASD. These findings suggest altered thalamic sensory gating which could be associated with an excitatory/inhibitory neurochemical imbalance, but such thalamic neurochemistry has never been examined in relation to SOR. Here we utilized magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging to examine the relationship between thalamic and somatosensory cortex inhibitory (gamma-aminobutyric acid, GABA) and excitatory (glutamate) neurochemicals with the intrinsic functional connectivity of those regions in 35 ASD and 35 typically developing pediatric subjects. Although there were no diagnostic group differences in neurochemical concentrations in either region, within the ASD group, SOR severity correlated negatively with thalamic GABA (r = −0.48, p < 0.05) and positively with somatosensory glutamate (r = 0.68, p < 0.01). Further, in the ASD group, thalamic GABA concentration predicted altered connectivity with regions previously implicated in SOR. These variations in GABA and associated network connectivity in the ASD group highlight the potential role of GABA as a mechanism underlying individual differences in SOR, a major source of phenotypic heterogeneity in ASD. In ASD, abnormalities of the thalamic neurochemical balance could interfere with the thalamic role in integrating, relaying, and inhibiting attention to sensory information. These results have implications for future research and GABA-modulating pharmacologic interventions.


2021 ◽  
Vol 118 (52) ◽  
pp. e2112212118
Author(s):  
Jiseok Lee ◽  
Joanna Urban-Ciecko ◽  
Eunsol Park ◽  
Mo Zhu ◽  
Stephanie E. Myal ◽  
...  

Immediate-early gene (IEG) expression has been used to identify small neural ensembles linked to a particular experience, based on the principle that a selective subset of activated neurons will encode specific memories or behavioral responses. The majority of these studies have focused on “engrams” in higher-order brain areas where more abstract or convergent sensory information is represented, such as the hippocampus, prefrontal cortex, or amygdala. In primary sensory cortex, IEG expression can label neurons that are responsive to specific sensory stimuli, but experience-dependent shaping of neural ensembles marked by IEG expression has not been demonstrated. Here, we use a fosGFP transgenic mouse to longitudinally monitor in vivo expression of the activity-dependent gene c-fos in superficial layers (L2/3) of primary somatosensory cortex (S1) during a whisker-dependent learning task. We find that sensory association training does not detectably alter fosGFP expression in L2/3 neurons. Although training broadly enhances thalamocortical synaptic strength in pyramidal neurons, we find that synapses onto fosGFP+ neurons are not selectively increased by training; rather, synaptic strengthening is concentrated in fosGFP− neurons. Taken together, these data indicate that expression of the IEG reporter fosGFP does not facilitate identification of a learning-specific engram in L2/3 in barrel cortex during whisker-dependent sensory association learning.


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