Biology subjects

Sajid, M. S.

Publications and source records attributed to Sajid, M. S..

6 recordsLinked to original sources

bioRxiv2025

Subthalamic nucleus controls cautious action timing under threat

Adaptive goal-directed actions performed under the threat of punishment introduce a demand for caution, often expressed as delayed response timing that balances urgency against error risk by allowing more time for cognitive evaluation. Although this form of temporal regulation is essential for survival, its underlying neural mechanisms remain poorly understood. We show that glutamatergic neurons in the subthalamic nucleus (STN) regulate the timing of cued actions to avoid harm. Optogenetic activation of the STN, or its projections to the midbrain but not the globus pallidus, modulates action timing in a frequency-dependent manner, accelerating initiation to the extent that animals can no longer respond cautiously, defer actions, or stop initiated actions. These results show that the STN shapes goal-directed behavior by gating action-initiation timing, establishing its midbrain projections as a key circuit for balancing urgency and caution under threat. Significance statementThis work shows that activity in the subthalamic nucleus (STN) helps set the timing of actions triggered by warning cues. By activating STN neurons and their projections to the midbrain, we found that stimulation made animals respond faster, and high-frequency activation eliminated their ability to delay actions when caution was required or to withhold actions that would otherwise be punished. These findings highlight a key brain pathway that governs when actions are initiated, a function that is often disrupted in neurological and psychiatric disorders.

neuroscience↗

bioRxiv2025

Encoding without generation in the medial prefrontal cortex during cautious goal-directed actions

Adaptive behavior under threat requires deciding when to act and when to withhold action to avoid harm, often under conditions where movement, arousal, and task demand covary. Medial prefrontal cortex (mPFC) activity is widely associated with such control, yet it remains unclear whether this activity reflects causal action generation or broader evaluative processes shaped by behavioral state. Here, we combined fiber photometry, single-cell calcium imaging, mixed-effects modeling, and optogenetic inhibition to examine how GABAergic neurons in mouse mPFC represent cues, actions, and outcomes during a series of learned avoidance tasks of increasing complexity that promote cautious responding. By explicitly controlling for baseline activity and movement, we show that much apparent task-related activity in mPFC reflects movement and cue-evoked signals that are also present in a control cortical region, the visual cortex. mPFC GABAergic neurons showed little encoding of simple avoidance contingencies but broadly encoded punished outcomes. A small subset of neurons with strong movement sensitivity encoded more demanding avoidance contingencies requiring selection between action generation and deferment. For equivalent avoidance actions, distinct neuronal populations preferentially encoded either cue onset or the action. Despite this encoding, optogenetic inhibition of mPFC had minimal effects on the learning or performance of the different contingencies. These findings reveal a dissociation between neural encoding and causal necessity, indicating that mPFC GABAergic activity primarily reflects evaluative and contextual aspects of cautious avoidance behavior rather than direct control of action execution. Significance statementAvoiding danger often requires deciding when to act and when to hold back. The dorsomedial prefrontal cortex (mPFC) is widely assumed to support this control, yet the contributions of its neurons have remained unclear. Using neural population and single-neuron recordings together with targeted inhibition in mice performing learned threat-guided tasks, we show that GABAergic mPFC neurons are activated by cues, actions, and outcomes, but are not required for executing the behavior itself. These findings suggest that the mPFC primarily evaluates and contextualizes threat-motivated actions rather than generating them, highlighting a common mismatch between neural encoding and causal necessity.

neuroscience↗

bioRxiv2025

Knowledge, attitudes, and practices of para-veterinary workers about ticks and tick-borne diseases in three provinces of Pakistan

There is a high prevalence of tick infestation in Pakistani livestock, affecting more than 45% of the population of more than 200 million small and large ruminants. Most livestock farmers seek assistance from para-veterinary workers, who fall under the definition of Veterinary Paraprofessionals (VPPs), according to the World Organization for Animal Health (WOAH). There is a shortage of information concerning the awareness of these para-veterinary workers regarding tick control and management. This study aims to bridge this critical knowledge gap by conducting a cross-sectional survey that evaluates the knowledge, attitudes, and practices of para-veterinary workers about tick-borne diseases (TBDs) in Pakistan. Between March and August 2023, we conducted a web-based survey among para-veterinary workers recruited via email, text message, and face-to-face conversations. Poisson regression was used to identify factors associated with knowledge, attitude, and practice (KAP) scores related to TBDs. We received 118 responses from three provinces; only 27.9% (n = 33) responded that they had attended workshops related to ticks and TBDs. Attending workshops was associated with higher KAP scores. All section scores were correlated, and higher knowledge scores were significantly associated with lower odds of tick exposure. Our findings suggest that workshop attendance is important in increasing overall awareness and promoting better practices regarding TBDs.

scientific communication and education↗

bioRxiv2025

A Forebrain Hub for Cautious Actions via the Midbrain

Adaptive goal-directed behavior requires dynamic coordination of movement, motivation, and environmental cues. Among these, cautious actions, where animals adjust their behavior in anticipation of predictable threats, are essential for survival. Yet, their underlying neural mechanisms remain less well understood than those of appetitive behaviors, where caution plays little role. Using calcium imaging in freely moving mice we show that glutamatergic neurons in the subthalamic nucleus (STN) are robustly engaged by contraversive movement during cue-evoked avoidance and exploratory behavior. Model-based analyses controlling for movement and other covariates revealed that STN neurons additionally encode salient sensory cues, punished errors, and especially cautious responding, where their activity anticipates avoidance actions. Targeted lesions and optogenetic manipulations reveal that STN projections to the midbrain are necessary for executing cued avoidance. These findings identify a critical role for the STN in orchestrating adaptive goal-directed behavior by integrating sensory, motor, and punitive signals to guide timely, cautious actions via its midbrain projections. Significance statementThis study provides new insights into the neural pathways that mediate adaptive goal-directed behaviors in response to environmental cues, identifying a critical role for glutamatergic projections from the subthalamic nucleus (STN) to the midbrain. We show that STN activation encodes caution and is essential for cued goal-directed actions. These findings deepen our understanding of the circuits involved in cued goal-directed adaptive behaviors used to cope with contextual challenges, which are often altered by brain disorders.

neuroscience↗

bioRxiv2021

Post-injury born oligodendrocytes integrate into the glial scar and inhibit growth of regenerating axons by premature myelination

Pathologies of the central nervous system (CNS) white matter often result in permanent functional deficits because mature mammalian projection neurons fail to regenerate long-distance axons after injury. A major barrier to axonal regenerative research is that the CNS axons that regenerate in response to experimental treatments stall growth before reaching their post-synaptic targets. Here, we test the hypothesis that premature, de novo, myelination of regenerating axons stalls their growth, even after bypassing the glial scar. To test this hypothesis, first, we used single cell RNA-seq (scRNA-seq) and immunohistological analysis to investigate whether post-injury born oligodendrocytes integrate into the glial scar after optic nerve injury. Then, we used a multiple sclerosis model of demyelination concurrently with the stimulation of axon regeneration by Pten knockdown (KD) in projection neurons after optic nerve injury. We found that post-injury born oligodendrocytes integrate into the glial scar, where they are susceptible to the demyelination treatment, which prevented premature myelination, and thereby enhanced Pten KD-stimulated axon regeneration. We also present a website for comparing the gene expression of scRNA-seq-profiled optic nerve oligodendrocytes under physiological and pathophysiological conditions. SIGNIFICANCE STATEMENTMyelin debris from degenerating axons along with reactive astrocytes in the glial scar inhibit CNS axon regeneration. However, even with the recently developed experimental approaches which activate axons to regenerate passed the glial scar, almost all axons still stall growth before reaching their post-synaptic targets. Here, we show that post-injury born oligodendrocytes integrate into the glial scar, and that other than myelin debris, live oligodendrocytes prematurely myelinating the regenerating axons inhibit growth, even if the axons have already regenerated passed the glial scar.

neuroscience↗

bioRxiv2020

Tick-Borne bacterial and protozoan animal pathogens shape the native microbiome within Hyalomma anatolicum anatolicum and Rhipicephalus microplus tick vectors

BackgroundTicks vector a variety of bacterial, viral, and protozoan pathogens of public and animal health significance. Ticks also harbor a diverse community of microbes linked with their biological processes like hematophagy and hence vector competence. The interactions between bacterial and/or protozoan pathogens and their tick vector microbiome are yet to be investigated. In lieu of this, this study was designed to define the microbial composition of uninfected and infected Hyalomma (H.) anatolicum anatolicum and Rhipicephalus (R.) microplus tick species. Methodology/Principal findingsA total of 320 H. anatolicum and R. microplus were screened for the presence of the protozoan (Theileria sp.), and bacterial (Anaplasma marginale) pathogens by PCR. Subsequently, the microbiome of uninfected and infected individual H. anatolicum and R. microplus were analyzed. The highly conserved V1-V3 region of the 16S rRNA gene was sequenced using the MiSeq Illumina platform. The microbiome of female H. anatolicum anatolicum ticks was dominated by the endosymbiont Candidatus Midichloria mitochondrii (CMM) and Francisella-like endosymbiont (FLE) which were not affected by pathogen infection. Ehrlichia species was detected in A. marginale-infected male H. anatolicum anatolicum (6.2%) as opposed to the Theileria sp.-infected female H. anatolicum anatolicum. Coxiella sp. was also detected in uninfected (2.96%) and A. marginale-infected (4.25%), but not in Theileria sp.-infected R. microplus ticks. Analysis of the eukaryote composition in the respectively ticks also revealed the presence of operational taxonomic units (OTUs) belonging to Plasmodium (P.) falciparum in Theileria sp.-infected H. a. anatolicum and R. microplus ticks, while Hepatozoon americanum detected from Theileria sp.-infected and uninfected H. a. anatolicum. Conclusion and SignificanceThis study establishes the extent of the diversity of microbial community of two important tick species from Pakistan and also revealed the presence of Theileria and A. marginale and additional pathogenic bacteria that could be of public health significance. We hypothesized that infection with either a protozoan or bacterial pathogen will alter the microbial composition within these tick species. Interestingly, we reported the detection of the malarial parasite (P. falciparum) from ticks infected with the protozoan pathogen (Theileria sp.). Further validation experiments are required on endosymbionts and pathogens of ticks to investigate how they could be important in the epidemiology of human and animal pathogens.

zoology↗