Biology subjects

Dooley, J. C.

Publications and source records attributed to Dooley, J. C..

10 recordsLinked to original sources

bioRxiv2026

A stereotaxic atlas of primary cortical areas in the developing rat brain from postnatal days 8 to 20

Postnatal brain growth is non-linear, making precise stereotaxic targeting in the developing rat neocortex difficult without age-specific knowledge of cortical area locations. Traditional atlases visualize brain slices in the coronal plane, which can obscure top-down areal boundaries and sub-domains. To address these shortcomings, we created a developmental stereotaxic atlas that maps the neocortex of postnatal day (P) 8, P12, P16, and P20 in Sprague-Dawley and Long-Evans rats onto a coordinate grid. After using a stereotaxic device to create a grid of fluorescent probes, we extracted the brain, flattened neocortical tissue, and stained it for cytochrome oxidase, which is predominantly found in layer IV of primary cortical areas. Reconstructions of the primary somatosensory, auditory, and visual cortices demonstrate high structural reproducibility within each age and strain group. Our atlas captures the location of primary cortical areas at these 4 ages, showing that neocortical expansion is non-isometric, expanding preferentially along the rostral-caudal axis. Finally, we complement these top-down maps by extracting local neocortical surface angles from an existing coronal atlas, enabling proper electrode orientation to be tangential to the developing neocortex. Ultimately, this anatomically verified resource provides a standardized blueprint that eliminates resource-intensive trial-and-error mapping and maximizes experimental reproducibility in developmental systems neuroscience. Significance StatementTargeting specific neocortical areas in developing rats is uniquely challenging because non-linear brain expansion renders scaled adult coordinates inaccurate, while traditional coronal sections obscure top-down areal boundaries. To resolve this, we established a top-down stereotaxic atlas that maps primary sensory cortices onto flattened, cytochrome oxidase-stained tissue across early postnatal development (P8-P20) in both Sprague-Dawley and Long-Evans rats. By combining equidistant coordinate grids with empirical cortical surface angles, this resource provides an accurate, reproducible surgical blueprint. This reference tool eliminates trial-and-error coordinate mapping, reduces animal waste, and maximizes experimental precision for the developmental neuroscience community.

neuroscience↗

bioRxiv2025

The developmental emergence of tonic and phasic REM sleep in rats

REM sleep is composed of two substates--phasic and tonic--that differ in their behavioral, sensory, and electrophysiological features. Although these substates are well characterized in adults, their developmental trajectory remains unclear. Here, we examined the development of tonic and phasic REM in rats from postnatal day (P) 12-24, spanning a period of rapid corticothalamic development. We recorded local field potentials and single units from primary motor cortex (M1), together with high-speed video and electromyographic recordings of the nuchal muscle. Periods of behavioral quiescence along with high delta power indicated NREM sleep, whereas periods of sustained muscle atonia and low delta power indicated REM sleep. At P16, M1 theta oscillations first appeared, and the delay to the first twitch increased, revealing the start of a distinct twitch-free portion of REM sleep. Motivated by this, we divided REM sleep into phasic and tonic periods, with and without twitching, respectively. Spiking activity and gamma power were consistently higher during phasic REM. At P20, phasic REM also showed faster theta oscillations than tonic REM. At P24, tonic REM was accompanied by a distinct alpha oscillation. These results show that the features distinguishing the two REM substates appear sequentially across development, revealing a progressive differentiation of REM sleep into tonic and phasic periods, a developmental refinement that may support increasingly complex forms of sleep-dependent plasticity. Significance StatementInfancy is marked by rapid circuit formation and by the dominance of REM sleep, a state thought to support early neural development. Yet sleep itself undergoes massive changes throughout this period, and the developmental timeline of REM sleep remains poorly understood. Using neural recordings and high-speed video from developing infant rats, we show that REM sleep gradually divides into two substates--tonic and phasic--across infancy. These substates exhibit age-dependent differences in movement, neural firing, and cortical oscillations, revealing increasing microstructural complexity in REM sleep. Our findings identify when these substates first emerge and how their defining features unfold over time, providing a framework for understanding how REM sleep supports developmental plasticity throughout early life.

neuroscience↗

bioRxiv2025

Subcortically generated movements activate motor cortex during sleep and wake in rats through postnatal day 24

The development of motor control in primary motor cortex (M1) requires both movement and neural activity. In rats, cortical motor control first appears around postnatal day (P) 25, prior to which movements are generated by subcortical motor nuclei such as the red nucleus (RN). While these subcortical movements are thought to provide the activity that guides the development of M1, the types of movements that drive M1 activity and their somatotopic and temporal precision remain unknown. Here, we recorded activity in the forelimb region of M1 of P12-24 rats as they cycled between sleep and wake, and compared M1 and RN activity in P24 rats. At every age, M1 neurons showed somatopically precise activity to REM sleep twitches, along with strong responses to wake movements. From P12 to P24, the proportion of neurons that showed twitch-related activity decreased, twitch-related activity became more temporally refined, and a larger fraction of spikes occurred before movement onset. At P24, M1 showed less premovement activity than RN. Further, in contrast to the non-selective activity seen in M1, some RN neurons showed selective movement-related activity during wake, firing only during particular wake movements. These findings reveal that movement-related activity in M1 is somatotopically precise by P12 and temporally precise by P24. But M1 still lacks the strong premovement activity and selectivity characteristic of RN, suggesting that at P24, subcortical outputs remain the main drivers of M1s movement-related activity. Significance StatementIn adults, primary motor cortex (M1) is widely recognized for its role in initiating voluntary movements and guiding motor learning. However, during early development, our findings show that M1 processes activity related to self-generated limb movements but does not drive the production of those movements. Using simultaneous recordings from M1 and the red nucleus (RN) of developing rats, we show that although M1 shows movement-related activity during wake and sleep, RN remains the principal driver of behavior through at least postnatal day 24. These results refine our understanding of early movement-related activity and highlight the possibility that both sleep-related twitches and wake movements shape sensorimotor development by driving neural activity in M1 and RN.

neuroscience↗

bioRxiv2023

The impact of prenatal alcohol and synthetic cannabinoid exposure on behavioral adaptations in adolescent offspring and alcohol self-administration in adulthood

Prenatal exposure to alcohol or cannabinoids can produce enduring neurobiological, cognitive, and behavioral changes in the offspring. Furthermore, prenatal co-exposure to alcohol and cannabinoids induces malformations in brain regions associated with reward and stress-related circuitry. This study examined the effects of co-exposure to alcohol and the synthetic cannabinoid (SCB) CP55,940 throughout gastrulation and neurulation in rats on basal corticosterone levels and a battery of behavioral tests during adolescence and alcohol self-administration in adulthood. Importantly, we find that prenatal alcohol exposure (PAE) caused lower baseline corticosterone levels in adolescent males and females. Co-exposure to alcohol + CP produced hyperactivity during open field test in males, but not females. During the two-bottle choice alcohol-drinking procedure, prenatal cannabinoid exposed male and female adolescent rats drank more alcohol than their vehicle-exposed controls. In adulthood, female rats treated with prenatal cannabinoid exposure (PCE), showed an overall total increase in alcohol intake during alcohol self-administration; but this was not found in males. When the reinforcer was changed to a 1% sucrose solution, male rats exposed to PCE, showed a reduced self-administration compared to vehicle-exposed males, potentially indicative of an anhedonic response. This lower self-administration persisted when 20% alcohol was reintroduced to the sucrose solution. Lastly, following an abstinence period, there were no changes due to prenatal drug exposure in either males or females. Overall, these data suggest lasting consequences of prenatal alcohol and cannabinoid exposure during adolescence and adulthood in male and female rats.

animal behavior and cognition↗

bioRxiv2022

Activity in developing prefrontal cortex is shaped by sleep and sensory experience

In developing rats, behavioral state exerts a profound modulatory influence on neural activity throughout the sensorimotor system, including primary motor cortex (M1). We hypothesized that similar state-dependent modulation occurs in higher-order cortical areas with which M1 forms functional connections. Here, using 8- and 12-day-old rats cycling freely between sleep and wake, we record neural activity in M1, secondary motor cortex (M2), and medial prefrontal cortex (mPFC). At both ages in all three areas, neural activity increased during active sleep (AS) compared with wake. Regardless of behavioral state, neural activity in M2 and mPFC increased during periods when limbs were moving. This movement-related activity in M2 and mPFC, like that in M1, is driven by sensory feedback. Our results, which diverge from those of previous studies using anesthetized pups, demonstrate that AS-dependent modulation and sensory responsivity extend to prefrontal cortex. These findings expand the range of factors shaping the activity-dependent development of higher-order cortical areas.

neuroscience↗

bioRxiv2021

Developmental onset of a cerebellar-dependent forward model of movement in motor thalamus

To execute complex behavior with temporal precision, adult animals use internal models to predict the sensory consequences of self-generated movement. Here, taking advantage of the unique kinematic features of twitches--the brief, discrete movements of active sleep--we captured the developmental onset of a cerebellar-dependent internal model. Using rats at postnatal days (P) 12, P16, and P20, we compared neural activity in two thalamic structures: the ventral posterior (VP) and ventral lateral (VL) nuclei, both of which receive somatosensory input but only the latter of which receives cerebellar input. At all ages, twitch-related activity in VP lagged behind movement, consistent with sensory processing; similar activity was observed in VL through P16. At P20, however, VL activity precisely mimicked the twitch itself, a pattern of activity that depended on cerebellar input. Altogether, these findings implicate twitches in the development and refinement of internal models of movement.

neuroscience↗

bioRxiv2021

Twitches emerge postnatally during quiet sleep in human infants and are synchronized with sleep spindles

SO_SCPLOWUMMARYC_SCPLOWIn humans and other mammals, the stillness of sleep is punctuated by bursts of rapid eye movements (REMs) and myoclonic twitches of the limbs [1]. Contrary to the notion that twitches are mere by-products of dreams, sensory feedback arising from twitching limbs provides a rich and unique source of activation to the developing sensorimotor system [2]. In fact, it is partly because of the behavioral activation of REM sleep that this state is also called active sleep (AS), in contrast with the behavioral quiescence that gives quiet sleep (QS)--the second major stage of sleep--its name. In human infants, for which AS occupies eight or more hours of each day [3], limb twitching is one among several components that help to identify the state [4-7]; nonetheless, we know relatively little about the structure and functions of twitching across development. Recently, in sleeping infants over the first seven postnatal months [8], we documented a pronounced shift in the temporal expression of twitching beginning around three months of age that suggested a qualitative shift in how twitches are produced. Here, we combine behavioral assessments of twitching with high-density electroencephalography (EEG) and demonstrate that this shift reflects the developmental emergence of limb twitches during QS. Twitches during QS are not only unaccompanied by REMs, but they also occur synchronously with sleep spindles, a hallmark of QS. As QS-related twitching increases with age, sleep spindle rate also increases along the sensorimotor strip. The emerging synchrony between subcortically generated twitches and cortical oscillations suggests the development of functional connectivity among distant sensorimotor structures, with potential implications for detecting and explaining atypical developmental trajectories.

neuroscience↗

bioRxiv2020

Sensory coding of limb kinematics in developing primary motor cortex

Primary motor cortex (M1) undergoes protracted development in mammals, functioning initially as a sensory structure. Throughout the first postnatal week in rats, M1 is strongly activated by self-generated forelimb movements--especially by the twitches that occur during active sleep. Here, we quantify the kinematic features of forelimb movements to reveal receptive-field properties of individual units within the forelimb region of M1. At postnatal day (P) 8, nearly all units were strongly modulated by movement amplitude, especially during active sleep. By P12, only a minority of units continued to exhibit amplitude-tuning, regardless of behavioral state. At both ages, movement direction also modulated M1 activity, though to a lesser extent. Finally, at P12, M1 population-level activity became more sparse and decorrelated, along with a substantial alteration in the statistical distribution of M1 responses to limb movements. These findings reveal a transition toward a more complex and informationally rich representation of movement long before M1 develops its motor functionality.

neuroscience↗

bioRxiv2020

Self-generated whisker movements drive state-dependent sensory input to developing barrel cortex

SO_SCPLOWUMMARYC_SCPLOWCortical development is an activity-dependent process [1-3]. Regarding the role of activity in developing somatosensory cortex, one persistent debate concerns the importance of sensory feedback from self-generated movements. Specifically, recent studies claim that cortical activity is generated intrinsically, independent of movement [3, 4]. However, other studies claim that behavioral state moderates the relationship between movement and cortical activity [5-7]. Thus, perhaps inattention to behavioral state leads to failures to detect movement-driven activity [8]. Here, we resolve this issue by associating local field activity (i.e., spindle bursts) and unit activity in the barrel cortex of 5-day-old rats with whisker movements during wake and myoclonic twitches of the whiskers during active (REM) sleep. Barrel activity increased significantly within 500 ms of whisker movements, especially after twitches. Also, higher-amplitude movements were more likely to trigger barrel activity; when we controlled for movement amplitude, barrel activity was again greater after a twitch than a wake movement. We then inverted the analysis to assess the likelihood that increases in barrel activity were preceded within 500 ms by whisker movements: At least 55% of barrel activity was attributable to sensory feedback from whisker movements. Finally, when periods with and without movement were compared, 70-75% of barrel activity was movement-related. These results confirm the importance of sensory feedback from movements in driving activity in sensorimotor cortex and underscore the necessity of monitoring sleep-wake states to ensure accurate assessments of the contributions of the sensory periphery to activity in developing somatosensory cortex.

neuroscience↗

bioRxiv2018

Developmental \"awakening\" of primary motor cortex to the sensory consequences of movement

Before primary motor cortex (M1) develops its motor functions, it functions like a somatosensory area. Here, by recording from neurons in the forelimb representation of M1 in postnatal day (P) 8-12 rats, we demonstrate a rapid shift in its sensory responses. At P8-10, M1 neurons respond overwhelmingly to feedback from sleep-related twitches of the forelimb, but the same neurons do not respond to wake-related movements. By P12, M1 neurons suddenly respond to wake movements, a transition that results from opening the sensory gate in the external cuneate nucleus. Also at P12, few M1 neurons respond to twitches, but the full complement of twitch-related feedback observed at P8 can be unmasked through local disinhibition. Finally, through P12, M1 sensory responses originate in the deep thalamorecipient layers, not primary somatosensory cortex. These findings demonstrate that M1 initially establishes a sensory framework upon which its later-emerging role in motor control is built.

neuroscience↗