Developmental and Adult Striatal Patterning of Nociceptin Ligand Marks Striosomal Population With Direct Dopamine Projections.

Circuit influences on the midbrain dopamine system are crucial to adaptive behavior and cognition. Recent developments in the study of neuropeptide systems have enabled high-resolution investigations of the intersection of neuromodulatory signals with basal ganglia circuitry, identifying the nociceptin/orphanin FQ (N/OFQ) endogenous opioid peptide system as a prospective regulator of striatal dopamine signaling. Using a prepronociceptin-Cre reporter mouse line, we characterized highly selective striosomal patterning of Pnoc mRNA expression in mouse dorsal striatum, reflecting the early developmental expression of Pnoc.

CalDAG-GEFI acts as a guanine nucleotide exchange factor for LRRK2 to regulate LRRK2 function and neurodegeneration.

Mutations in are the most common genetic cause of Parkinson's disease (PD). LRRK2 protein contains two enzymatic domains: a GTPase (Roc-COR) and a kinase domain. Disease-causing mutations are found in both domains.

Striosomes control dopamine via dual pathways paralleling canonical basal ganglia circuits.

Balanced activity of canonical direct D1 and indirect D2 basal ganglia pathways is considered a core requirement for normal movement, and their imbalance is an etiologic factor in movement and neuropsychiatric disorders. We present evidence for a conceptually equivalent pair of direct D1 and indirect D2 pathways that arise from striatal projection neurons (SPNs) of the striosome compartment rather than from SPNs of the matrix, as do the canonical pathways. These striosomal D1 (S-D1) and D2 (S-D2) pathways target substantia nigra dopamine-containing neurons instead of basal ganglia motor output nuclei.

Dopamine release plateau and outcome signals in dorsal striatum contrast with classic reinforcement learning formulations.

We recorded dopamine release signals in centromedial and centrolateral sectors of the striatum as mice learned consecutive versions of visual cue-outcome conditioning tasks. Dopamine release responses differed for the centromedial and centrolateral sites. In neither sector could these be accounted for by classic reinforcement learning alone as classically applied to the activity of nigral dopamine-containing neurons.

Social good reappraisal as a novel and effective emotion regulation strategy.

Society asks individuals, such as front-line medical and emergency personnel or social media moderators, to help others under highly negative emotional circumstances, and those individuals need to regulate their emotions for their own well being. A well-studied form of emotion regulation is reappraisal, the use of cognitive processes used to reinterpret initial emotional responses to negative events. Distancing (pretending that a situation is distant in time or space) is well documented to be an effective form of emotion regulation, but it may not be applicable in social contexts where individuals must engage with distressing events to help others.

Striosomes Target Nigral Dopamine-Containing Neurons via Direct-D1 and Indirect-D2 Pathways Paralleling Classic Direct-Indirect Basal Ganglia Systems.

Balanced activity of canonical direct D1 and indirect D2 basal ganglia pathways is considered a core requirement for normal movement, and their imbalance is an etiologic factor in movement and neuropsychiatric disorders. We present evidence for a conceptually equivalent pair of direct-D1 and indirect-D2 pathways that arise from striatal projection neurons (SPNs) of the striosome compartment rather than from SPNs of the matrix, as do the canonical pathways. These S-D1 and S-D2 striosomal pathways target substantia nigra dopamine-containing neurons instead of basal ganglia motor output nuclei.

Representation of rhythmic chunking in striatum of mice executing complex continuous movement sequences.

We used a step-wheel system to examine the activity of striatal projection neurons as mice practiced stepping on complexly arranged foothold pegs in this Ferris-wheel-like device to receive reward. Sets of dorsolateral striatal projection neurons were sensitive to specific parameters of repetitive motor coordination during the runs. They responded to combinations of the parameters of continuous movements (interval, phase, and repetition), forming "chunking responses"-some for combinations of these parameters across multiple body parts.

Simultaneous two-photon imaging and wireless EEG recording in mice.

Background: In vivo two-photon imaging is a reliable method with high spatial resolution that allows observation of individual neuron and dendritic activity longitudinally. Neurons in local brain regions can be influenced by global brain states such as levels of arousal and attention that change over relatively short time scales, such as minutes. As such, the scientific rigor of investigating regional neuronal activities could be enhanced by considering the global brain state.

Dispositional mindfulness: Dissociable affective and cognitive processes.

Mindfulness has been linked to a range of positive social-emotional and cognitive outcomes, but the underlying mechanisms are unclear. As one of the few traits or dispositions that are associated with both affective and cognitive benefits, we asked whether mindfulness is associated with affective and cognitive outcomes through a shared, unitary process or through two dissociable processes. We examined this in adolescents using behavioral measures and also reanalyzed previously reported neuroimaging findings relating mindfulness training to either affect (negative emotion, stress) or cognition (sustained attention).

Daily positive and negative affect during the COVID-19 pandemic.

The COVID-19 pandemic influenced emotional experiences globally. We examined daily positive and negative affect between May/June 2020 and February 2021 (N = 151,049; 3,509,982 observations) using a convenience sample from a national mobile application-based survey that asked for daily affect reports. Four questions were examined: (1) How did people in the United States feel from May/June 2020 to February 2021?; (2) What demographic variables are related to positive and negative affect?; (3) What is the relationship between experienced stressors and daily affect?; and (4) What is the relationship between daily affect and preventive behavior? Positive affect increased, and negative decreased over time.

Synchronous Measurements of Extracellular Action Potentials and Neurochemical Activity with Carbon Fiber Electrodes in Nonhuman Primates.

Measuring the dynamic relationship between neuromodulators, such as dopamine, and neuronal action potentials is imperative to understand how these fundamental modes of neural signaling interact to mediate behavior. Here, we developed methods to measure concurrently dopamine and extracellular action potentials (i.e.

The endocannabinoid N-arachidonoyl dopamine is critical for hyperalgesia induced by chronic sleep disruption.

Chronic pain is highly prevalent and is linked to a broad range of comorbidities, including sleep disorders. Epidemiological and clinical evidence suggests that chronic sleep disruption (CSD) leads to heightened pain sensitivity, referred to as CSD-induced hyperalgesia. However, the underlying mechanisms are unclear.

Scalable, flexible carbon fiber electrode thread arrays for three-dimensional probing of neurochemical activity in deep brain structures of rodents.

We developed a flexible "electrode-thread" array for recording dopamine neurochemicals from a lateral distribution of subcortical targets (up to 16) transverse to the axis of insertion. Ultrathin (∼10 μm diameter) carbon fiber (CF) electrode-threads (CFETs) are clustered into a tight bundle to introduce them into the brain from a single-entry point. The individual CFETs splay laterally in deep brain tissue during insertion due to their innate flexibility.

Preliteracy Skills Mediate the Relation Between Early Speech Sound Production and Subsequent Reading Outcomes.

Purpose: Learning to read is a complex, multifaceted process that relies on several speech and language-related subskills. Individual differences in word reading outcomes are indicated among children with inaccurate speech sound productions, with some of these children developing later reading difficulties. There are inconsistent reports as to whether phonological deficits and/or weaknesses in oral language explain these subsequent reading difficulties.

Emergence of rhythmic chunking in complex stepping of mice.

Motor chunking is important for motor execution, allowing atomization and efficiency of movement sequences. However, it remains unclear why and how chunks contribute to motor execution. To analyze the structure of naturally occurring chunks, we trained mice to run in a complex series of steps and identified the formation of chunks.

Foramen lacerum impingement of trigeminal nerve root as a rodent model for trigeminal neuralgia.

Trigeminal neuralgia (TN) is a classic neuralgic pain condition with distinct clinical characteristics. Modeling TN in rodents is challenging. Recently, we found that a foramen in the rodent skull base, the foramen lacerum, provides direct access to the trigeminal nerve root.

Speech- and language-linked FOXP2 mutation targets protein motors in striatal neurons.

Human speech and language are among the most complex motor and cognitive abilities. The discovery of a mutation in the transcription factor FOXP2 in KE family members with speech disturbances has been a landmark example of the genetic control of vocal communication in humans. Cellular mechanisms underlying this control have remained unclear.

Striosomes and Matrisomes: Scaffolds for Dynamic Coupling of Volition and Action.

Striosomes form neurochemically specialized compartments of the striatum embedded in a large matrix made up of modules called matrisomes. Striosome-matrix architecture is multiplexed with the canonical direct-indirect organization of the striatum. Striosomal functions remain to be fully clarified, but key information is emerging.

Diminished Repetition Suppression Reveals Selective and Systems-Level Face Processing Differences in ASD.

Repeated exposure to a stimulus results in reduced neural response, or repetition suppression, in brain regions responsible for processing that stimulus. This rapid accommodation to repetition is thought to underlie learning, stimulus selectivity, and strengthening of perceptual expectations. Importantly, reduced sensitivity to repetition has been identified in several neurodevelopmental, learning, and psychiatric disorders, including autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by challenges in social communication and repetitive behaviors and restricted interests.

Highly synchronized cortical circuit dynamics mediate spontaneous pain in mice.

Cortical neural dynamics mediate information processing for the cerebral cortex, which is implicated in fundamental biological processes such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes the cortical network into an aberrant state and, if so, whether it can be brought back to a "normal" operating range to ameliorate pain are unknown.

Effects of acute and repeated administration of the selective M PAM VU0152099 on cocaine versus food choice in male rats.

Ligands that stimulate muscarinic acetylcholine receptors 1 and 4 (M , M ) have shown promising effects as putative pharmacotherapy for cocaine use disorder in rodent assays. We have previously shown reductions in cocaine effects with acute M stimulation, as well as long-lasting, delayed reductions in cocaine taking and cocaine seeking with combined M /M receptor stimulation or with M stimulation alone. M stimulation opposes dopaminergic signalling acutely, but direct dopamine receptor antagonists have proved unhelpful in managing cocaine use disorder because they lose efficacy with long-term administration.

Functional mapping and cooperation between the cerebellum and cerebrum during word reading.

Multiple areas in the cerebellum have been reported to be engaged in reading. However, how these regions cooperate with the reading-related areas in the cerebrum remains unclear. Here, brain images of fifty-two adults were acquired via functional magnetic resonance imaging.

Categorical perception and influence of attention on neural consistency in response to speech sounds in adults with dyslexia.

Developmental dyslexia is a common neurodevelopmental disorder that is associated with alterations in the behavioral and neural processing of speech sounds, but the scope and nature of that association is uncertain. It has been proposed that more variable auditory processing could underlie some of the core deficits in this disorder. In the current study, magnetoencephalography (MEG) data were acquired from adults with and without dyslexia while they passively listened to or actively categorized tokens from a /ba/-/da/ consonant continuum.

The Role of the Dorsal-Lateral Prefrontal Cortex in Reward Sensitivity During Approach-Avoidance Conflict.

Approach-Avoidance conflict (AAC) arises from decisions with embedded positive and negative outcomes, such that approaching leads to reward and punishment and avoiding to neither. Despite its importance, the field lacks a mechanistic understanding of which regions are driving avoidance behavior during conflict. In the current task, we utilized transcranial magnetic stimulation (TMS) and drift-diffusion modeling to investigate the role of one of the most prominent regions relevant to AAC-the dorsolateral prefrontal cortex (dlPFC).