Sensory driven activity during early life is critical for setting up the proper connectivity of the sensory cortices. We ask here if social play behavior, a particular form of social interaction that is highly abundant during post-weaning development, is equally important for setting up connections in the developing prefrontal cortex (PFC). Young male rats were deprived from social play with peers during the period in life when social play behavior normally peaks (postnatal day 21-42; SPD rats), followed by resocialization until adulthood. We recorded synaptic currents in layer 5 cells in slices from medial PFC of adult SPD and control rats and observed that inhibitory synaptic currents were reduced in SPD slices, while excitatory synaptic currents were unaffected. This was associated with a decrease in perisomatic inhibitory synapses from parvalbumin-positive GABAergic cells. In parallel experiments, adult SPD rats achieved more reversals in a probabilistic reversal learning task (PRL), which depends on t...

Two structurally connected brain regions are more likely to interact, with the lengths of the structural bundles, their widths, myelination, and the topology of the structural connectome influencing the timing of the interactions. We introduce an in vivo approach for measuring functional delays across the whole brain in humans (of either sex) using magneto/electroencephalography and integrating them with the structural bundles. The resulting topochronic map of the functional delays/velocities shows that larger bundles have faster velocities. We estimated the topochronic map in multiple sclerosis patients, who have damaged myelin sheaths, and controls, demonstrating greater delays in patients across the network and that structurally lesioned tracts were slowed down more than unaffected ones. We provide a novel framework for estimating functional transmission delays in vivo at the single-subject and single-tract level. SIGNIFICANCE STATEMENT: This manuscript provides a straightforward way to estimate pati...

Ventral tegmental area (VTA) dopaminergic neurons, which are well known for their central roles in reward and motivation-related behaviors, have been shown to participate in itch processing via their projection to the nucleus accumbens (NAc). However, the functional roles of different dopamine receptor subtypes in subregions of the NAc during itch processing remain unknown. With pharmacological approaches, we found that the blockade of dopamine D1 receptors (D1R), but not dopamine D2 receptors (D2R), in the lateral shell (LaSh) of the NAc impaired pruritogen-induced scratching behavior in male mice. In contrast, pharmacological activation of D2R in both the LaSh and medial shell (MeSh) of the NAc attenuated the scratching behavior induced by pruritogens. Consistently, we found that dopamine release, as detected by a dopamine sensor, was elevated in the LaSh rather than the MeSh of the NAc at the onset of scratching behavior. Furthermore, the elevation of dopamine release in the LaSh of the NAc persisted ev...

Detecting object boundaries is crucial for recognition, but how the process unfolds in visual cortex remains unknown. To study the problem faced by a hypothetical boundary cell, and to predict how cortical circuitry could produce a boundary cell from a population of conventional “simple cells”, we labeled 30,000 natural image patches and used Bayes’ rule to help determine how a simple cell should influence a nearby boundary cell depending on its relative offset in receptive field position and orientation. We identified three basic types of cell-cell interactions: rising and falling interactions with a range of slopes and saturation rates, as well as non-monotonic (bump-shaped) interactions with varying modes and amplitudes. Using simple models we show that a ubiquitous cortical circuit motif consisting of direct excitation and indirect inhibition – a compound effect we call "incitation" – can produce the entire spectrum of simple cell-boundary cell interactions found in our dataset. Moreover, we show that ...

Running wheels for mice residing in the home cage are useful for the continuous measurement of locomotor activity for studies testing exercise interventions or exercise-induced effects on brain and metabolism. Here, we have developed an open source, printable, open-faced running wheel that is automated to collect locomotor information such as distance travelled, wheel direction, and velocity that can be binned into epochs over 24 h or multiple days. This system allows for remote data collection to avoid human interference in mouse behavioural experiments. We tested this system in an activity-based-anorexia procedure. Using these wheels, we replicate previous findings that food restriction augments wheel running activity. Significance statement Anorexia Nervosa (AN) is a psychiatric disease with few treatments and a high mortality rate. It is important to better understand the biology to accelerate the development of new therapies. The most used animal model to study AN is the activity-based anorexia mod...

Adaptive control is the online adjustment of behavior to guide and optimize responses after errors or conflict. The neural circuits involved in monitoring and adapting behavioral performance following error are poorly understood. The prefrontal cortex (PFC) plays a critical role in this form of control. However, these brain areas are densely connected with many other regions and it is unknown which projections are critical for adaptive behavior. Here, we tested the involvement of four distinct dorsal and ventral prefrontal cortical projections to striatal and thalamic target areas in adaptive control. We re-analyzed data from published experiments, using trial-by-trial analyses of behavior in an operant task for attention and impulsivity. We find that male rats slow their responses and perform worse following errors. Moreover, by combining retrograde labeling and chemogenetic silencing, we find that dorsomedial prefrontal pyramidal neurons that project to the lateral nucleus of the mediodorsal thalamus (MD...

In Parkinson’s Disease (PD) patients and rodent models, dopaminergic neuron loss (DAN) results in severe motor disabilities. In contrast, general motility is preserved after early postnatal DAN loss in rodents. Here we used mice of both sexes to show that the preserved motility observed after early DAN loss depends on functional changes taking place in medium spiny neurons (MSN) of the dorsomedial striatum (DMS) that belong to the direct pathway (dMSN). Previous animal model studies showed that adult loss of dopaminergic input depresses dMSN response to cortical input, which likely contributes to PD motor impairments. However, the response of DMS-dMSN to their preferred medial prefrontal cortex input is preserved after neonatal DAN loss as shown by in vivo studies. Moreover, their response to inputs from adjacent cortical areas is increased, resulting in reduced cortical inputs selectivity. Additional ex vivo studies show that membrane excitability increases in dMSN. Furthermore, chemogenetic inhibition of...

It is well known that recent sensory experience influences perception, recently demonstrated by a phenomenon termed “serial dependence”. However, its underlying neural mechanisms are poorly understood. We measured ERP responses to pairs of stimuli presented randomly to the left or right hemifield. 17 male and female adults judged whether the upper or lower half of the grating had higher spatial frequency, independently of the horizontal position of the grating. This design allowed us to trace the memory signal modulating task performance and also the implicit memory signal associated with hemispheric position. Using classification techniques, we decoded the position of the current, previous stimuli and response from voltage scalp distributions of the current trial. Classification of previous responses reached full significance only 700 ms after presentation of current stimulus, consistent with retrieval of an activity-silent memory trace. Cross-condition classification accuracy of past responses (trained o...

It is well known that recent sensory experience influences perception, recently demonstrated by a phenomenon termed “serial dependence”. However, its underlying neural mechanisms are poorly understood. We measured ERP responses to pairs of stimuli presented randomly to the left or right hemifield. 17 male and female adults judged whether the upper or lower half of the grating had higher spatial frequency, independently of the horizontal position of the grating. This design allowed us to trace the memory signal modulating task performance and also the implicit memory signal associated with hemispheric position. Using classification techniques, we decoded the position of the current, previous stimuli and response from voltage scalp distributions of the current trial. Classification of previous responses reached full significance only 700 ms after presentation of current stimulus, consistent with retrieval of an activity-silent memory trace. Cross-condition classification accuracy of past responses (trained o...