Implicit sequence and visuomotor skill learning is important for successful goal-directed behavior in everyday tasks. However, prior research has primarily relied on correlational methods to investigate the underlying neural mechanisms of sequence and visuomotor skill learning. To evaluate the necessary contributions of different motor cortical regions to both types of skill learning, we enrolled 62 neurotypical adults (41 female, 21 male) and delivered spatiotemporally resolved single-pulse transcranial magnetic stimulation (TMS) over either the premotor cortex (PMC) or primary motor cortex (M1) to transiently disrupt activity while participants practiced an implicit motor sequence task. We hypothesized that 1) PMC disruption would preferentially reduce sequence-specific skill acquisition (Experiment 1) and retention (Experiment 2) while 2) M1 disruption would diminish visuomotor skill acquisition and retention but not sequence learning. Our results demonstrated that TMS-based interference over both M1 an...

Vocal communication is essential for social behavior, yet the distributed brain networks underlying vocal production remain elusive. Male mice produce ultrasonic vocalizations (USVs) during courtship, providing a rodent model for investigating neural circuits underlying innate vocal communication. Here, we used a double-labelling strategy that combined genetic activity tagging (TRAP2) and c-Fos immunohistochemistry to generate an unbiased, whole-brain map of neuronal ensembles activated during courtship-induced USV production in adult male mice. By tracking neuronal activity across 25 brain regions during two independent courtship sessions, we identified populations consistently recruited during social vocalization. Quantitative analyses revealed robust activation in the caudal periaqueductal gray, confirming its established role as a hub for vocal motor control. Importantly, correlation analyses between neuronal activity and USV count distinguished regions specifically linked to vocal output from those as...

Organizing a “Nano” is a fantastic opportunity to network and connect with others in your field. Don’t know how to organize a nanosymposium or find others to participate? This webinar will review how to select a topic, identify others who might be interested in joining, and how to recruit others to join the nano.

The suprachiasmatic nucleus (SCN) produces diffusible signals sufficient to sustain circadian locomotor rhythms, although the nature of such signals, their targets, and the pathway whereby such signals may travel is unknown. It is possible that the venous portal veins that connect the capillary beds of the SCN to those of the organum vasculosum of the lamina terminalis (OVLT) provide a vascular pathway whereby signals originating in SCN neurons can reach local targets in the OVLT. Given the presence of the blood–brain interface (BBI) within the SCN, it is unclear how diffusible signals originating in SCN neurons might access the capillary vasculature of this nucleus. Estimates of astrocyte coverage of capillary vasculature range widely, from 70 to 100%, and furthermore such coverage can change dynamically. In the present study, we investigated whether three vasoactive peptidergic processes found in the mouse SCN, namely, vasopressin, vasoactive intestinal peptide, and gastrin-releasing peptide, might breac...

The refinement of gross motor skills, such as locomotion, during development is conserved across vertebrate species. Our previous work demonstrated, in larval zebrafish, that dopaminergic signaling through the dopamine D2-like family of receptors, specifically the dopamine 4 receptor subtype, was necessary for the developmental transformation of behaviorally relevant locomotor activity from an immature to a mature pattern between 3 and 4 d postfertilization. In this study, we used a complement of tools, including electrophysiology, pharmacology, in vivo calcium imaging, liquid chromatography-mass spectrometry, and quantitative reverse transcription polymerase chain reaction to characterize the functional and molecular mechanisms responsible for this dopaminergic-mediated refinement of spinal locomotor activity. The results demonstrate that the dopamine 4 receptor subtype is functional in, at least, a subset of immature larvae. Further, gene expression of all D2-like receptor subtypes, levels of dopamine, a...

Animal learning can be analyzed on two timescales: task acquisition across training sessions and motivation fluctuations within training sessions. How do variations in motor and neurophysiologic activity relate to task performance over these timescales? Here, this question was examined in head-fixed mice performing a whisker-based sensory discrimination task. Male mice were trained for 12–14 daily sessions on a go/no-go task, each lasting ∼1 h to capture spontaneous performance fluctuations over minutes. Simultaneous to task performance, “nonperformance variables” were tracked, including wheel running, pupil size, eyelid aperture, and sensory cortical activity. First, motivation states were defined based on performance tendencies over minutes, leading to three state categories: persistent, disengaged, or attentive. Nonperformance variables were found to predict these states independent of task correctness. Then, when further parsing these states by the go/no-go outcomes of hit, miss, false alarm, or correc...

Dopamine D1 receptor (D1R) signaling in the brain has been strongly implicated in multiple cognitive processes, with D1 agonists known to enhance performance. The development of functionally selective D1 agonists that differentially activate D1R-mediated cAMP versus β-arrestin signaling may offer precision therapy if we understand how signaling bias impacts integrated cognitive processes in complex tasks. We therefore examined the effects of two selective D1 agonists, 2-methyldihydrexidine (2MDHX) and PF-06256142 (PF), on a rodent touchscreen-based Trial-Unique Nonmatching-To-Location task. Primarily assessing both spatial working memory and pattern separation in adult male rats, this behavioral paradigm requires greater cognitive demands to maintain performance throughout the testing session, significantly increasing task complexity. Our results revealed an inverted U-shaped dose response curve for both compounds, aligning with our previously published work, but did not demonstrate marked improvement in t...

With repeated exposure to addictive drugs, there is a shift from drug abuse to drug addiction that is mediated by the transition from goal-directed to habitual control. It is well known that the development of habitual control over behavior relies upon cell-type-specific synaptic changes in both D1 and D2 medium spiny neurons (MSNs) in dorsal striatum. Specifically, habitual behavior is mediated by increased synaptic strength in D1 and D2 MSNs in dorsolateral striatum (DLS), suggesting similar cell-type-specific synaptic changes may underlie the development of habitual cocaine-seeking behavior. However, cell-type-specific synaptic changes have not been evaluated in DLS in this context. Therefore, we trained male rats to self-administer cocaine in a self-administration paradigm that allows for differentiation of goal-directed versus habitual cocaine-seeking behavior. Moreover, we used a viral vector under a D2-specific promoter to fluorescently label D2 MSNs with eYFP in DLS. Evoked excitatory postsynaptic ...

Vocal communication is essential for social behavior, yet the distributed brain networks underlying vocal production remain elusive. Male mice produce ultrasonic vocalizations (USVs) during courtship, providing a rodent model for investigating neural circuits underlying innate vocal communication. Here, we used a double-labeling strategy combining genetic activity tagging (TRAP2) and c-Fos immunohistochemistry to generate an unbiased, whole-brain map of neuronal ensembles activated during courtship-induced USV production in adult male mice. By tracking neuronal activity across 25 brain regions during two independent courtship sessions, we identified populations consistently recruited during social vocalization. Quantitative analyses revealed robust activation in the caudal periaqueductal gray, confirming its established role as a hub for vocal motor control. Importantly, correlation analyses between neuronal activity and USV count distinguished regions specifically linked to vocal output from those associa...

Decision-making is a continuous process that manifests as evolving sequences of motor movements while animals navigate the sensory environment. Studying decision-making in a naturalistic setting has been challenging as restrictions are typically imposed on subjects’ motor actions in the laboratory. We utilized a novel paradigm in which animals move freely throughout the decision-making process to examine the sequence and timing of motor actions predictive of decisions. We trained freely moving ferrets (two males, three females), highly visual carnivores, to perform visual discrimination tasks and measured their head position and eye movements to assess the temporal dynamics of heading and saccades during visually guided decisions. We discovered that heading revealed ferrets' “turning time” per trial, signaling their choices, and heading on its own best predicted ferrets' decisions. Ferrets made decisions quickly and decisively, although total trial durations varied across animals. Importantly, initial head...