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Waiblinger, C.

Publications and source records attributed to Waiblinger, C..

4 recordsLinked to original sources

The engagement of layer 6 corticothalamic neurons in somatosensation

The corticothalamic neurons from layer 6 (L6CT) of primary sensory cortices provide extensive input to the thalamus in addition to projecting within the cortex, positioning them to play a key hypothesized role in shaping thalamocortical signaling. With the expansion of tools for precise functional identification of L6CT neurons for in-vivo electrophysiology, increasing evidence highlights L6CT neurons as dynamic gain modulators of thalamocortical sensory responses. However much of the work to date has been conducted under anesthesia and not in the context of awake and/or behaving animals. In this study, we show that L6CT neurons in the awake mouse convey information about ascending sensory inputs, the timing of which is fast enough to contribute to the sensory response of neurons throughout the thalamocortical circuit. Overall, L6CT neurons robustly encode the presence vs absence of a sensory stimulus but are relatively weak encoders of the fine details. Benchmarked against the activity of other excitatory cortical neuron, we also provide evidence for L6CT neurons as predictors of the behavioral outcome during a trained detection task. Taken together, the results in this study tie L6CT neurons to behavior in tactile detection, one of the most fundamental functional roles of the pathway.

neuroscience↗

Sensory-Behavioral Deficits in Parkinson's Disease: Insights from a 6-OHDA Mouse Model

Parkinsons disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta, leading to dopamine depletion in the striatum and the hallmark motor symptoms of the disease. However, non-motor deficits, particularly sensory symptoms, often precede motor manifestations, offering a potential early diagnostic window. The impact of non-motor deficits on sensation behavior and the underlying mechanisms remain poorly understood. In this study, we examined changes in tactile sensation within a parkinsonian state by employing a mouse model of PD induced by 6-hydroxydopamine (6-OHDA) to deplete striatal DA. Leveraging the conserved mouse whisker system as a model for tactile-sensory stimulation, we conducted psychophysical experiments to assess sensory-driven behavioral performance during a tactile detection task in both the healthy and PD-like state. Our findings reveal a range of deficits across subjects following 6-OHDA lesion, including DA loss, motor asymmetry, weight loss, and varying levels of altered tactile sensation behavior. Behavioral changes ranged from no impairments in minor cases to isolated sensory-behavioral deficits in moderate cases and severe motor dysfunction in advanced stages. These results underscore the complex relationship between DA imbalance and sensory-motor processing, emphasizing the need for precise and multifaceted behavioral measurements to accurately capture the diverse manifestations of PD. SIGNIFICANCE STATEMENTThis study explores sensory-motor aspects of Parkinsons disease using a 6-OHDA mouse model. Leveraging the mouse whisker system, we reveal diverse deficits in tactile sensation behavior due to dopamine depletion. Our findings emphasize the importance of sensory assessments in understanding the diverse spectrum of PD symptoms.

neuroscience↗

Adaptive Behavior and the Role of Primary Somatosensory Cortex

Behavioral experience and flexibility are crucial for survival in a constantly changing environment. Despite evolutionary pressures to develop adaptive behavioral strategies in a dynamically changing sensory landscape, the underlying neural correlates have not been well explored. Here, we use genetically encoded voltage imaging to measure signals in primary somatosensory cortex (S1) during sensory learning and behavioral adaptation in the mouse. In response to changing stimulus statistics, mice adopt a strategy that modifies their detection behavior in a context dependent manner as to maintain reward expectation. Surprisingly, neuronal activity in S1 shifts from simply representing stimulus properties to transducing signals necessary for adaptive behavior in an experience dependent manner. Our results suggest that neuronal signals in S1 are part of an adaptive framework that facilitates flexible behavior as individuals gain experience, which could be part of a general scheme that dynamically distributes the neural correlates of behavior during learning.

neuroscience↗

Unilateral optogenetic inhibition and excitation of basal ganglia output show opposing effects on left/right lick choices and movement initiation in mice

Models of basal ganglia function predict that tonic inhibitory output to motor thalamus suppresses unwanted movements, and that a decrease in such activity leads to action selection. A direct test of these outcomes of thalamic inhibition has not been performed, however. To conduct such a direct test, we utilized rapid optogenetic activation and inactivation of the GABAergic output of the substantia nigra pars reticulata (SNr) to motor thalamus in mice that were trained in a sensory cued left/right licking task. Directional licking tasks have previously been shown to depend on a thalamocortical feedback loop between ventromedial motor thalamus and antero-lateral premotor cortex (Li et al., 2015; Guo et al., 2017). In confirmation of model predictions, we found that 1s of unilateral optogenetic inhibition of GABAergic output from the SNr biased decision making towards the contralateral lick spout with ipsilaterally cued trials while leaving motor performance intact. In contrast, 1s of optogenetic excitation of SNr terminals in motor thalamus resulted in an opposite bias towards the ipsilateral direction confirming a bidirectional effect of tonic nigral output on directional decision making. In a second variant of the task we disallowed anticipatory licking and found that successful suppression of anticipatory licking was also impacted by our optogenetic manipulations in agreement with the suppressive effect of tonic nigral output. Nevertheless, direct unilateral excitation of SNr cell bodies resulted in bilateral movement suppression, suggesting that descending motor pathways from the SNr to superior colliculus also play an important role in the control of licking behavior.\n\nSignificance StatementThis study provides the first evidence that basal ganglia output to motor thalamus can control decision making in left/right licking choices and suppress anticipatory movement initiation. Unilateral optogenetic inhibition or excitation of basal ganglia output via the substantia nigra resulted in opposite changes of directional lick choices and could override the sensory information on lick direction provided by a whisker stimulus. These results suggest that basal ganglia output gates activity in a thalamo-cortical feedback loop previously shown to underlie the control of forced choice directional licking behavior. The results substantiate models stating that tonic inhibition of motor thalamus from the basal ganglia directs action selection and suppresses unwanted movements.

neuroscience↗