The perception of dynamic visual stimuli relies on two apparently conflicting perceptual mechanisms: rapid visual input must sometimes be integrated into unitary percepts but at other times must be segregated or parsed into separate objects or events. Though they have opposite effects on our perceptual experience, the deployment of spatial attention benefits both operations. Little is known about the neural mechanisms underlying this impact of spatial attention on temporal perception. Here, we record magnetoencephalography (MEG) in male and female humans to demonstrate that the deployment of spatial attention for the purpose of segregating or integrating visual stimuli impacts prestimulus oscillatory activity in retinotopic visual brain areas where the attended location is represented. Alpha band oscillations contralateral to an attended location are therefore faster than ipsilateral oscillations when stimuli appearing at this location will need to be segregated, but slower in expectation of the need for i...

Midfrontal theta (FMθ) in the human EEG is commonly viewed as a generic and homogeneous mechanism of cognitive control in general and conflict processing in particular. However, the role of FMθ in approach–avoidance conflicts and its cross-task relationship to simpler stimulus-response conflicts remain to be examined more closely. Therefore, we recorded EEG data while 59 healthy participants (49 female, 10 male) completed both an approach–avoidance task and a flanker task. Participants showed significant increases in FMθ power in response to conflicts in both tasks. To our knowledge, this is the first study to show a direct relationship between FMθ and approach–avoidance conflicts. Crucially, FMθ activity was task dependent and showed no cross-task correlation. To assess the possibility of multiple FMθ sources, we applied source separation [generalized eigendecomposition (GED)] to distinguish independent FMθ generators. The activity of the components showed a similar pattern and was again task specific. Ho...

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...

Mutations in PTEN-induced kinase 1 (PINK1) contribute to autosomal recessive Parkinson's disease with cognitive and neuropsychiatric comorbidities. Disturbances in dendritic and spine architecture are hallmarks of neurodegenerative and neuropsychiatric conditions, but little is known of the impact of PINK1 on these structures. We used Pink1 −/− mice to study the role of endogenous PINK1 in regulating dendritic architecture, spine density, and spine maturation. Pink1 −/− cortical neurons of unknown sex showed decreased dendritic arborization, affecting both apical and basal arbors. Dendritic simplification in Pink1 −/− neurons was primarily driven by diminished branching with smaller effects on branch lengths. Pink1 −/− neurons showed reduced spine density with a shift in morphology to favor filopodia at the expense of mushroom spines. Electrophysiology revealed significant reductions in miniature EPSC (mEPSC) frequency in Pink1 −/− neurons, consistent with the observation of decreased spine numbers. Transf...

Autism is characterized by two key diagnostic criteria including social deficits and repetitive behaviors. Although recent studies implicated ventral striatum in social deficits and dorsal striatum in repetitive behaviors, here we revealed coexisting and opposite morphologic and functional alterations in the dorsostriatal direct and indirect pathways, and such alterations in these two pathways were found to be responsible, respectively, for the two abovementioned different autism-like behaviors exhibited by male mice prenatally exposed to valproate. The alteration in direct pathway was characterized by a potentiated state of basal activity, with impairment in transient responsiveness of D1-MSNs during social exploration. Concurrent alteration in indirect pathway was a depressed state of basal activity, with enhancement in transient responsiveness of D2-MSNs during repetitive behaviors. A causal relationship linking such differential alterations in these two pathways to the coexistence of these two autism-l...

Oxytocin (OXT) and OXT receptor (OXTR)-mediated signaling control excitability, firing patterns, and plasticity of hippocampal CA2 pyramidal neurons, which are pivotal in generation of brain oscillations and social memory. Nonetheless, the ionic mechanisms underlying OXTR-induced effects in CA2 neurons are not fully understood. Using slice physiology in a reporter mouse line and interleaved current-clamp and voltage-clamp experiments, we systematically identified the ion channels modulated by OXT signaling in CA2 pyramidal cells (PYRs) in mice of both sexes and explored how changes in channel conductance support altered electrical activity. Activation of OXTRs inhibits an outward potassium current mediated by inward rectifier potassium channels ( I Kir) and thus favoring membrane depolarization. Concomitantly, OXT signaling also diminishes inward current mediated by hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels ( I h), providing a hyperpolarizing drive. The combined reduction in both I...

The midbrain periaqueductal gray (PAG) plays a central role in pain modulation via descending pathways. Opioids and cannabinoids are thought to activate these descending pathways by relieving intrinsic GABAergic inhibition of PAG neurons which project to the rostroventromedial medulla (RVM), a process known as disinhibition. However, the PAG also receives descending extrinsic GABAergic inputs from the central nucleus of the amygdala (CeA) which are thought to inhibit PAG GABAergic interneurons. It remains unclear how opioids and cannabinoids act at these different synapses to control descending analgesic pathways. We used optogenetics, tract tracing and electrophysiology to identify the circuitry underlying opioid and cannabinoid actions within the PAG of male and female rats. It was observed that both RVM-projection and nonprojection PAG neurons received intrinsic-PAG and extrinsic-CeA synaptic inputs, which were predominantly GABAergic. Opioids acted via presynaptic µ-receptors to suppress both intrinsic...

Forelimb-related areas of the motor cortex communicate directly to downstream areas in the brainstem and spinal cord via axons that project to and through the pyramidal tract (PT). To better understand the diversity of the brainstem branching patterns of these pyramidal tract projections, we used MAPseq, a molecular barcode technique for population-scale sampling with single-axon resolution. In experiments using mice of both sexes, we first confirmed prior results demonstrating the basic efficacy of axonal barcode identification of primary motor cortex (M1) PT-type axons, including corticobulbar (CBULB) and corticospinal (CSPI) subclasses. We then used multiplexed MAPseq to analyze projections from M1 and M2 (caudal and rostral forelimb areas). The four basic axon subclasses comprising these projections (M1-CSPI, M1-CBULB, M2-CSPI, M2-CBULB) showed a complex mix of differences and similarities in their brainstem projection profiles. This included relatively abundant branching by all classes in the dorsal m...