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Biology subjects

SheikhBahaei, S.

Publications and source records attributed to SheikhBahaei, S..

7 recordsLinked to original sources

On Breathing Variability in the Tree Shrew

Tree shrews (Tupaia belangeri) are increasingly used in comparative neuroscience, yet their respiratory physiology remains poorly characterized. We quantified spontaneous breathing and respiratory rhythm variability in awake adult tree shrews (n = 10; 5 males, 5 females) using whole-body plethysmography. Respiratory frequency decreased by approximately 16% with acclimatization to the recording chamber, while respiratory timing, body-mass-normalized respiratory amplitude, inspiratory flow, and minute ventilation remained relatively stable. After acclimatization, mean respiratory parameters were similar between sexes, but short-term breath-to-breath variability (SD1) was greater in males than females, whereas SD2 was comparable. These findings establish baseline respiratory characteristics in awake tree shrews and identify sex-dependent differences in short-term respiratory rhythm stability.

neuroscience↗

A stuttering-associated Gnptab variant alters fine-motor kinematics

Precise reach-to-grasp movements rely on complex cortico-basal ganglia and cerebellar circuits, and can be affected by cellular pathway defects. We investigated whether mild Gnptab deficiency, affecting mannose-6-phosphate-dependent lysosomal enzyme targeting, impairs fine motor behaviors in mice. Using the staircase test, high-frame-rate video, and markerless tracking, we assessed reaching and grasping in Gnptab-mutant and control littermates. Our data suggest that Gnptab-mutant mice retrieved about 75% fewer pellets than controls and exhibited abnormal grasping, characterized by increased wrist extension and larger digit angles, decreased digital velocity, and shorter reach distances, while elbow angles remained largely unchanged. These findings suggest a specific deficit in grasp shaping and trajectory control, rather than overall limb positioning. Our data establishes a quantitative link between GNPTAB-related lysosomal pathway disruption and fine-motor impairments, providing a valuable model for understanding how cellular dysfunction impacts motor circuit function.

neuroscience↗

Non-vocal motor deficits in a transgenic mouse model linked to stuttering disorders

Stuttering is a neurodevelopmental disorder characterized by involuntary disruptions in speech. In addition, non-vocal motor impairments are reported in some individuals who stutter. Although its precise cause remains unknown, mutations in lysosomal trafficking proteins (such as GNPTAB) have been identified in a subgroup of people who stutter. To understand the functional significance of these mutations, transgenic Gnptab mice have been developed, and as expected, these mice exhibit vocal deficits throughout developmental stages. However, whether these mice also display non-vocal motor impairments is unknown. Our data reveal deficits in the breathing, locomotion, and grooming behaviors of the Gnptab mouse model, outlining a broader phenotype linked to GNPTAB mutations in stuttering. These findings suggest that lysosomal dysfunction may disrupt astrocyte-regulated motor circuits, affecting both vocal and non-vocal rhythmic behaviors that are central to stuttering neurophysiological symptoms.

genetics↗

Morphological deficits of glial cells in a transgenic mouse model for developmental stuttering

Vocal production involves intricate neural coordination across various brain regions. Stuttering, a common speech disorder, has genetic underpinnings, including mutations in lysosomal-targeting pathway genes. Using a Gnptab-mutant mouse model linked to stuttering, we examined neuron and glial cell morphology in vocal production circuits. Our findings revealed altered astrocyte and microglia processes in these circuits in Gnptab-mutant mice, while control regions remained unaffected. Our results shed light on the potential role of glial cells in stuttering pathophysiology and highlight their relevance in modulating vocal production behaviors.

cell biology↗

Brainstem astrocytes regulate breathing and may affect arousal state in rats

Variations in arousal levels can impact respiratory patterns. However, whether changes in breathing behaviors can influence arousal state is not fully understood. In this study, we investigated the role of astrocytes in the preBotzinger complex (preBotC) in modulating arousal states via breathing in adult conscious rats. Using viral vector tools, we selectively interfered with astrocytic signaling in the preBotC. Rats with inhibited astrocytic signaling exhibited slower breathing rates and behaviors indicative of a calmer state, whereas enhanced purinergic signaling in preBotC astrocytes led to faster breathing and heightened arousal. Our findings reveal a key role for astrocyte-mediated mechanism in the preBotC that influences both respiratory behaviors and higher-order brain functions like arousal, suggesting a bidirectional link between breathing behaviors and mental states. Highlights- In this study, we used molecular approaches to interfere with vesicular signaling in preBotC astrocytes. - We showed that inhibiting vesicular release mechanisms in preBotC astrocytes are associated with calm behaviors: lower breathing and sigh rates, and longer sniffing time. - We showed that enhancing vesicular release mechanisms in preBotC astrocytes are associated with more aroused behaviors: higher breathing and sigh rates as well as shorter sniffing time.

physiology↗

Whole-brain analysis of CO2 chemosensitive regions and identification of the retrotrapezoid and medullary raphe nuclei in the common marmoset (Callithrix jacchus)

Respiratory chemosensitivity is an important mechanism by which the brain senses changes in blood partial pressure of CO2 (PCO2). It is proposed that special neurons (and astrocytes) in various brainstem regions play key roles as CO2 central respiratory chemosensors in rodents. Although common marmosets (Callithrix jacchus), New-World non-human primates, show similar respiratory responses to elevated inspired CO2 as rodents, the chemosensitive regions in marmoset brain have not been defined yet. Here, we used c-fos immunostainings to identify brain-wide CO2-activated brain regions in common marmosets. In addition, we mapped the location of the retrotrapezoid nucleus (RTN) and raphe nuclei in the marmoset brainstem based on colocalization of CO2-induced c-fos immunoreactivity with Phox2b, and TPH immunostaining, respectively. Our data also indicated that, similar to rodents, marmoset RTN astrocytes express Phox2b and have complex processes that create a meshwork structure at the ventral surface of medulla. Our data highlight some cellular and structural regional similarities in brainstem of the common marmosets and rodents.

physiology↗

Breathing Behaviors in Common Marmoset (Callithrix jacchus)

The respiratory system maintains homeostatic levels of oxygen (O2) and carbon dioxide (CO2) in the body through rapid and efficient regulation of frequency and depth (tidal volume) of breathing. Many studies on homeostatic control of breathing have been done on rodent animal models, in which they have relatively reduced chemosensitivities when compared with primates. The use of common marmoset (Callithrix jacchus), a New World non-human primate model, in neuroscience is increasing, however, the data on their breathing is limited and their respiratory behaviors have yet to be characterized. Using Whole-body Plethysmography in room air as well as in hypoxic (low O2) and hypercapnic (high CO2) conditions, we defined breathing behaviors in awake, freely behaving marmosets. Additionally, we optimized an analysis toolkit for unsupervised analysis of respiratory activities in common marmoset. Our data indicate that marmosets exposure to hypoxia decreased metabolic rate and increased sigh rate. However, the hypoxic condition did not augment the ventilatory response. Hypercapnia, on the other hand, increased both the frequency and tidal volume. In this study, we described breathing behaviors of common marmosets in a variety of O2 and CO2 conditions.

neuroscience↗