Inhibitory control of synaptic signals preceding locomotion in mouse frontal cortex.
Ontology highlight
ABSTRACT:
SUBMITTER: Zhang CL
PROVIDER: S-EPMC8640223 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Genome-wide expression profiling of the human brain has revealed genes that are differentially expressed across the lifespan. Characterizing these genes adds to our understanding of both normal functions and pathological conditions. Additionally, the specific cell-types that contribute to the motor, sensory and cognitive declines during aging are unclear. Here we test if age-related genes show higher expression in specific neural cell types. Our study leverages data from two sources of murine single-cell expression data and two sources of age-associations from large gene expression studies of postmortem human brain. We used nonparametric gene set analysis to test for age-related enrichment of genes associated with specific cell-types; we also restricted our analyses to specific gene ontology groups. Our analyses focused on a primary pair of single-cell expression data from the mouse visual cortex and age-related human post-mortem gene expression information from the orbitofrontal cortex. Additional pairings that used data from the hippocampus, prefrontal cortex, somatosensory cortex and blood were used to validate and test specificity of our findings. We found robust age-related up-regulation of genes that are highly expressed in oligodendrocytes and astrocytes, while genes highly expressed in layer 2/3 glutamatergic neurons were down-regulated across age. Genes not specific to any neural cell type were also down-regulated, possibly due to the bulk tissue source of the age-related genes. A gene ontology-driven dissection of the cell-type enriched genes highlighted the strong down-regulation of genes involved in synaptic transmission and cell-cell signaling in the Somatostatin (Sst) neuron subtype that expresses the cyclin dependent kinase 6 (Cdk6) and in the vasoactive intestinal peptide (Vip) neuron subtype expressing myosin binding protein C, slow type (Mybpc1). These findings provide new insights into cell specific susceptibility to normal aging, and suggest age-related synaptic changes in specific inhibitory neuron subtypes.
| S-EPMC5446995 | biostudies-literature
Project description:Push-pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull-push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull-push influence on excitatory neurons-an inversion of the canonical push-pull of feedforward input.
| S-EPMC5967235 | biostudies-literature
Project description:The brain constantly generates predictions about the environment to guide action. Unexpected events lead to surprise and can necessitate the modification of ongoing behavior. Surprise can occur for any sensory domain, but it is not clear how these separate surprise signals are integrated to affect motor output. By applying a trial-to-trial Bayesian surprise model to human electroencephalography data recorded during a cross-modal oddball task, we tested whether there are separate predictive models for different sensory modalities (visual, auditory), or whether expectations are integrated across modalities such that surprise in one modality decreases surprise for a subsequent unexpected event in the other modality. We found that while surprise was represented in a common frontal signature across sensory modalities (the fronto-central P3 event-related potential), the single-trial amplitudes of this signature more closely conformed to a model with separate surprise terms for each sensory domain. We then investigated whether surprise-related fronto-central P3 activity indexes the rapid inhibitory control of ongoing behavior after surprise, as suggested by recent theories. Confirming this prediction, the fronto-central P3 amplitude after both auditory and visual unexpected events was highly correlated with the fronto-central P3 found after stop-signals (measured in a separate stop-signal task). Moreover, surprise-related and stopping-related activity loaded onto the same component in a cross-task independent components analysis. Together, these findings suggest that medial frontal cortex maintains separate predictive models for different sensory domains, but engages a common mechanism for inhibitory control of behavior regardless of the source of surprise.
| S-EPMC6687204 | biostudies-literature
Project description:The brain can combine auditory and visual information to localize objects. However, the cortical substrates underlying audiovisual integration remain uncertain. Here, we show that mouse frontal cortex combines auditory and visual evidence; that this combination is additive, mirroring behavior; and that it evolves with learning. We trained mice in an audiovisual localization task. Inactivating frontal cortex impaired responses to either sensory modality, while inactivating visual or parietal cortex affected only visual stimuli. Recordings from >14,000 neurons indicated that after task learning, activity in the anterior part of frontal area MOs (secondary motor cortex) additively encodes visual and auditory signals, consistent with the mice's behavioral strategy. An accumulator model applied to these sensory representations reproduced the observed choices and reaction times. These results suggest that frontal cortex adapts through learning to combine evidence across sensory cortices, providing a signal that is transformed into a binary decision by a downstream accumulator.
| S-EPMC10957398 | biostudies-literature
Project description:Growing evidence indicates that responses in sensory cortex are modulated by factors beyond direct sensory stimulation. In primary visual cortex (V1), for instance, responses increase with locomotion. Here we show that this increase is accompanied by a profound change in spatial integration. We recorded from V1 neurons in head-fixed mice placed on a spherical treadmill. We characterized spatial integration and found that the responses of most neurons were suppressed by large stimuli. As in primates, this surround suppression increased with stimulus contrast. These effects were captured by a divisive normalization model, where the numerator originates from a central region driving the neuron and the denominator originates from a larger suppressive field. We then studied the effects of locomotion and found that it markedly reduced surround suppression, allowing V1 neurons to integrate over larger regions of visual space. Locomotion had two main effects: it increased spontaneous activity, and it weakened the suppressive signals mediating normalization, relative to the driving signals. We conclude that a fundamental aspect of visual processing, spatial integration, is controlled by an apparently unrelated factor, locomotion. This control might operate through the mechanisms that are in place to deliver surround suppression.
| S-EPMC3661981 | biostudies-literature
Project description:The cingulo-opercular network (including the dorsal anterior cingulate and bilateral anterior insula) shows 3 distinct task-control signals across a wide variety of tasks, including trial-related signals that appear to come online at or near the end of the trial. Previous work suggests that there are separable responses in this network for errors and ambiguity, implicating multiple types of processing units within these regions. Using a unique paradigm, we directly show that these separable responses withhold activity to the end of the trial, in the service of reporting performance back into the task set. Participants performed a slow reveal task where images were presented behind a black mask which was gradually degraded, and they pressed a button when they could recognize the object that was being revealed. A behavioral pilot was used to identify ambiguous stimuli. We found interactive effects of accuracy and ambiguity, which suggests that these regions are computing and utilizing information, at one time, about both types of performance indices. Importantly, we showed a relationship between cingulo-opercular activity and behavioral performance, suggesting a role for these regions in performance reporting, per se. We discuss these results in the context of task control.
| S-EPMC6059248 | biostudies-literature
Project description:The frontal eye field (FEF) is one of several cortical regions thought to modulate sensory inputs. Moreover, several hypotheses suggest that the FEF can only modulate early visual areas in the presence of a visual stimulus. To test for bottom-up gating of frontal signals, we microstimulated subregions in the FEF of two monkeys and measured the effects throughout the brain with functional magnetic resonance imaging. The activity of higher-order visual areas was strongly modulated by FEF stimulation, independent of visual stimulation. In contrast, FEF stimulation induced a topographically specific pattern of enhancement and suppression in early visual areas, but only in the presence of a visual stimulus. Modulation strength depended on stimulus contrast and on the presence of distractors. We conclude that bottom-up activation is needed to enable top-down modulation of early visual cortex and that stimulus saliency determines the strength of this modulation.
| S-EPMC3011100 | biostudies-literature
Project description:Cognitive control of action is associated with conscious effort and is hypothesised to be reflected by increased frontal theta activity. However, the functional role of these increases in theta power, and how they contribute to cognitive control remains unknown. We conducted an MEG study to test the hypothesis that frontal theta oscillations interact with sensorimotor signals in order to produce controlled behaviour, and that the strength of these interactions will vary with the amount of control required. We measured neuromagnetic activity in 16 healthy adults performing a response inhibition (Go/Switch) task, known from previous work to modulate cognitive control requirements using hidden patterns of Go and Switch cues. Learning was confirmed by reduced reaction times (RT) to patterned compared to random Switch cues. Concurrent measures of pupil diameter revealed changes in subjective cognitive effort with stimulus probability, even in the absence of measurable behavioural differences, revealing instances of covert variations in cognitive effort. Significant theta oscillations were found in five frontal brain regions, with theta power in the right middle frontal and right premotor cortices parametrically increasing with cognitive effort. Similar increases in oscillatory power were also observed in motor cortical gamma, suggesting an interaction. Right middle frontal and right precentral theta activity predicted changes in pupil diameter across all experimental conditions, demonstrating a close relationship between frontal theta increases and cognitive control. Although no theta-gamma cross-frequency coupling was found, long-range theta phase coherence among the five significant sources between bilateral middle frontal, right inferior frontal, and bilateral premotor areas was found, thus providing a mechanism for the relay of cognitive control between frontal and motor areas via theta signalling. Furthermore, this provides the first evidence for the sensitivity of frontal theta oscillations to implicit motor learning and its effects on cognitive load. More generally these results present a possible a mechanism for this frontal theta network to coordinate response preparation, inhibition and execution.
| S-EPMC8727746 | biostudies-literature
Project description:Predictive coding (PC) has been suggested as one of the main mechanisms used by brains to interact with complex environments. PC theories posit top-down prediction signals, which are compared with actual outcomes, yielding in turn prediction error (PE) signals, which are used, bottom-up, to modify the ensuing predictions. However, disentangling prediction from PE signals has been challenging. Critically, while many studies found indirect evidence for PC in the form of PE signals, direct evidence for the prediction signal is mostly lacking. Here, we provide clear evidence, obtained from intracranial cortical recordings in human surgical patients, that the human lateral prefrontal cortex evinces prediction signals while anticipating an event. Patients listened to task-irrelevant sequences of repetitive tones including infrequent predictable or unpredictable pitch deviants. The broadband high-frequency amplitude (HFA) was decreased prior to the onset of expected relative to unexpected deviants in the frontal cortex only, and its amplitude was sensitive to the increasing likelihood of deviants following longer trains of standards in the unpredictable condition. Single-trial HFA predicted deviations and correlated with poststimulus response to deviations. These results provide direct evidence for frontal cortex prediction signals independent of PE signals.
| S-EPMC7963121 | biostudies-literature
Project description:The inferior colliculus (IC) is the major midbrain auditory integration center, where virtually all ascending auditory inputs converge. Although the IC has been extensively studied for sound processing, little is known about the neural activity of the IC in moving subjects, as frequently happens in natural hearing conditions. Here, by recording neural activity in walking mice, we show that the activity of IC neurons is strongly modulated by locomotion, even in the absence of sound stimuli. Similar modulation was also found in hearing-impaired mice, demonstrating that IC neurons receive non-auditory, locomotion-related neural signals. Sound-evoked activity was attenuated during locomotion, and this attenuation increased frequency selectivity across the neuronal population, while maintaining preferred frequencies. Our results suggest that during behavior, integrating movement-related and auditory information is an essential aspect of sound processing in the IC.
| S-EPMC7004561 | biostudies-literature