Increased level of kynurenic acid is thought to contribute to the development of cognitive deficits in schizophrenia through an α7nAChR-mediated mechanism in the prefrontal cortex (PFC). However, it remains unclear to what extent disruption of PFC α7nAChR signaling impacts afferent transmission and its modulation of behavior. Using male rats, we found that PFC infusion of methyllycaconitine (MLA; α7nAChR antagonist) shifts ventral hippocampal-induced local field potential (LFP) suppression to LFP facilitation, an effect only observed in adults. Hippocampal stimulation can also elicit a GluN2B-mediated LFP potentiation (when PFC GABAAR is blocked) that is insensitive to MLA. Conversely, PFC infusion of MLA diminished the gain of amygdalar transmission, which is already enabled by postnatal day (P)30. Behaviorally, the impact of prefrontal MLA on trace fear-conditioning and extinction was also age related. While freezing behavior during conditioning was reduced by MLA only in adults, it elicited opposite eff...

Attending to a stimulus enhances the neuronal responses to it, while responses to nonattended stimuli are not enhanced and may even be suppressed. Although the neural mechanisms of response enhancement for attended stimuli have been intensely studied, the neural mechanisms underlying attentional suppression remain largely unknown. It is uncertain whether attention acts to suppress the processing in sensory cortical areas that would otherwise process the nonattended stimulus or the subcortical input to these cortical areas. Moreover, the neurochemical mechanisms inducing a reduction or suppression of neuronal responses to nonattended stimuli are as yet unknown. Here, we investigated how attention directed toward visual processing cross-modally acts to suppress vestibular responses in the human brain. By using functional magnetic resonance spectroscopy in a group of female and male subjects, we find that attention to visual motion downregulates in a load-dependent manner the concentration of excitatory neuro...

Julien Catanese and Dieter Jaeger (see pages [1878–1891][1]) The basal ganglia participate with cortex and thalamus in recurrent regulatory loops that promote particular movements and inhibit premature or inappropriate movements. The output nuclei of the basal ganglia, including the substantia

Neuronal firing patterns are crucial to underpin circuit level behaviors. In cerebellar Purkinje cells (PCs), both spike rates and pauses are used for behavioral coding, but the cellular mechanisms causing code transitions remain unknown. We use a well-validated PC model to explore the coding strategy that individual PCs use to process parallel fiber (PF) inputs. We find increasing input intensity shifts PCs from linear rate-coders to burst-pause timing-coders by triggering localized dendritic spikes. We validate dendritic spike properties with experimental data, elucidate spiking mechanisms, and predict spiking thresholds with and without inhibition. Both linear and burst-pause computations use individual branches as computational units, which challenges the traditional view of PCs as linear point neurons. Dendritic spike thresholds can be regulated by voltage state, compartmentalized channel modulation, between-branch interaction and synaptic inhibition to expand the dynamic range of linear computation o...

Animals can categorize the environment into “states,” defined by unique sets of available action-outcome contingencies in different contexts. Doing so helps them choose appropriate actions and make accurate outcome predictions when in each given state. State maps have been hypothesized to be held in the orbitofrontal cortex (OFC), an area implicated in decision-making and encoding information about outcome predictions. Here we recorded neural activity in OFC in 6 male rats to test state representations. Rats were trained on an odor-guided choice task consisting of five trial blocks containing distinct sets of action-outcome contingencies, constituting states, with unsignaled transitions between them. OFC neural ensembles were analyzed using decoding algorithms. Results indicate that the vast majority of OFC neurons contributed to representations of the current state at any point in time, independent of odor cues and reward delivery, even at the level of individual neurons. Across state transitions, these r...

The primary motor hand area (M1HAND) and adjacent dorsal premotor cortex (PMd) form the so-called motor hand knob in the precentral gyrus. M1HAND and PMd are critical for dexterous hand use and are densely inter-connected via cortico-cortical axons, lacking a sharp demarcating border. In 24 young right-handed volunteers, we performed multi-modal mapping to delineate the relationship between structure and function in the right motor hand knob. Quantitative structural magnetic resonance imaging (MRI) at 3 Tesla yielded regional R1-maps as a proxy of cortical myelin content. Participants also underwent functional MRI. We mapped task-related activation and temporal precision, while they performed a visuo-motor synchronization task requiring visually cued abduction movements with the left index or little finger. We also performed sulcus-aligned transcranial magnetic stimulation (TMS) of the motor hand knob to localize the optimal site (hotspot) for evoking a motor evoked potential (MEP) in two intrinsic hand mu...

Past work has demonstrated that active suppression of salient distractors is a critical part of visual selection. Evidence for goal-driven suppression includes below-baseline visual encoding at the position of salient distractors (Gaspelin and Luck, 2015) and neural signals such as the Pd that track the position and number of distractors in the visual field (Feldmann-Wustefeld and Vogel, 2019). One basic question regarding distractor suppression is whether it is inherently spatial or nonspatial in character. Indeed, past work has shown that distractors evoke both spatial (Theeuwes, 1992) and nonspatial forms of interference (Folk and Remington, 1998), motivating a direct examination of whether space is integral to goal-driven distractor suppression. Here, we use behavioral and EEG data from adult humans (male and female) to provide clear evidence for a spatial gradient of suppression surrounding salient singleton distractors. Replicating past work, both reaction time and neural indices of target selection ...

Learning the spatial layout of a novel environment is associated with dynamic activity changes in the hippocampus and in medial parietal areas. With advancing age, the ability to learn spatial environments deteriorates substantially but the underlying neural mechanisms are not well understood. Here, we report findings from a behavioral and a fMRI experiment where healthy human older and younger adults of either sex performed a spatial learning task in a photorealistic virtual environment. We modeled individual learning states using a Bayesian state-space model and found that activity in retrosplenial cortex/parieto-occipital sulcus and anterior hippocampus did not change systematically as a function learning in older compared to younger adults across repeated episodes in the environment. Moreover, effective connectivity analyses revealed that the age-related learning deficits were linked to an increase in hippocampal excitability. Together, these results provide novel insights into how human aging affects ...

The neural mechanisms that allow animals to adapt their previously learned associations in response to changes in the environment remain poorly understood. To probe the synaptic mechanisms that mediate such adaptive behavior, we trained mice on an auditory-motor reversal task, and tracked changes in the strength of corticostriatal synapses associated with the formation of learned associations. Using a ChR2-based electrophysiological assay in acute striatal slices, we measured the strength of these synapses after animals learned to pair auditory stimuli with specific actions. Here, we report that the pattern of synaptic strength initially established by learning remains unchanged even when the task contingencies are reversed. Our findings reveal that synaptic changes associated with the initial acquisition of this task are not erased or overwritten, and that behavioral reversal of learned associations may recruit a separate neural circuit. These results suggest a more complex role of the striatum in regulat...

Computer vision approaches have made significant inroads into offline tracking of behavior and estimating animal poses. In particular, because of their versatility, deep-learning approaches have been gaining attention in behavioral tracking without any markers. Here, we developed an approach using DeepLabCut for real-time estimation of movement. We trained a deep-neural network (DNN) offline with high-speed video data of a mouse whisking, then transferred the trained network to work with the same mouse, whisking in real-time. With this approach, we tracked the tips of three whiskers in an arc and converted positions into a TTL output within behavioral time scales, i.e., 10.5 ms. With this approach, it is possible to trigger output based on movement of individual whiskers, or on the distance between adjacent whiskers. Flexible closed-loop systems like the one we have deployed here can complement optogenetic approaches and can be used to directly manipulate the relationship between movement and neural activity.