Biology subjects

Fouda, S.

Publications and source records attributed to Fouda, S..

3 recordsLinked to original sources

bioRxiv2024

Multiple Functions of Cerebello-Thalamic Neurons in Learning and Offline Consolidation of a Motor Skill in mice.

Motor skill learning is a complex and gradual process that involves the cortex and basal ganglia, both crucial for the acquisition and long-term retention of skills. The cerebellum, which rapidly learns to adjust the movement, connects to the motor cortex and the striatum primarily via the ventral and intralaminar thalamus respectively. Here, we evaluated the contribution of cerebellar neurons projecting to these thalamic nuclei in a skilled locomotion task in mice. Using a targeted chemogenetic inhibition that preserves the motor abilities, we found that cerebellar nuclei neurons projecting to the intralaminar thalamus contribute to learning and expression, while cerebellar nuclei neurons projecting to the ventral thalamus contribute to offline consolidation. Asymptotic performance, however, required each type of neurons. Thus, our results show that cerebellar neurons belonging to two parallel cerebello-thalamic pathways play distinct, but complementary, roles functioning on different timescales and both necessary for motor skill learning.

neuroscience↗

bioRxiv2022

Smaller total and subregional cerebellar volumes in posttraumatic stress disorder: a mega-analysis by the ENIGMA-PGC PTSD workgroup

BackgroundThe cerebellum critically contributes to higher-order cognitive and emotional functions such fear learning and memory. Prior research on cerebellar volume in PTSD is scant and has neglected neuroanatomical subdivisions of the cerebellum that differentially map on to motor, cognitive, and affective functions. MethodsWe quantified cerebellar lobule volumes using structural magnetic resonance imaging in 4,215 adults (PTSD n= 1640; Control n=2575) across 40 sites from the from the ENIGMA-PGC PTSD working group. Using a new state-of-the-art deep-learning based approach for automatic cerebellar parcellation, we obtained volumetric estimates for the total cerebellum and 28 subregions. Linear mixed effects models controlling for age, gender, intracranial volume, and site were used to compare cerebellum total and subregional volume in PTSD compared to healthy controls. The Benjamini-Hochberg procedure was used to control the false discovery rate (p-FDR < .05). ResultsPTSD was associated with significant grey and white matter reductions of the cerebellum. Compared to controls, people with PTSD demonstrated smaller total cerebellum volume. In addition, people with PTSD showed reduced volume in subregions primarily within the posterior lobe (lobule VIIB, crus II), but also the vermis (VI, VIII), flocculonodular lobe (lobule X), and cerebellar white matter (all p-FDR < 0.05). Effects of PTSD on volume were consistent, and generally more robust, when examining symptom severity rather than diagnostic status. ConclusionsThese findings implicate regionally specific cerebellar volumetric differences in the pathophysiology of PTSD. The cerebellum appears to play an important role in high-order cognitive and emotional processes, far beyond its historical association with vestibulomotor function. Further examination of the cerebellum in trauma-related psychopathology will help to clarify how cerebellar structure and function may disrupt cognitive and affective processes at the center of translational models for PTSD.

neuroscience↗

bioRxiv2020

Effects of optogenetic stimulation of basal forebrain parvalbumin neurons on Alzheimer's disease pathology

Neuronal activity can modify Alzheimers disease pathology. Although overexcitation of neurons can facilitate disease progression, the induction of cortical gamma oscillations can reduce amyloid load and improve cognitive functions in mouse models. These beneficial effects of gamma oscillations can be caused by either optogenetic activation of cortical parvalbumin-positive (PV+) neurons or 40 Hz repetitive sensory stimuli. However, given the fact that cortical gamma oscillations can be induced by multiple mechanisms, it is still unclear whether other approaches to induce gamma oscillations can also be beneficial. Here we show that optogenetic activation of PV+ neurons in the basal forebrain (BF) increases amyloid burden, rather than reducing it. We applied 40 Hz optical stimulation in the BF of 5xFAD mice by expressing channelrhodopsin-2 (ChR2) in PV+ neurons. After one-hour induction of cortical gamma oscillations over three days, we observed the increase in the concentration of amyloid-{beta}42 in the frontal cortical region, but not amyloid-{beta}40. The density of amyloid plaques also increased in the medial prefrontal cortex and the septal nuclei, both of which are targets of BF PV+ neurons. These results suggest that effects of cortical gamma oscillations on Alzheimers disease pathology can be bidirectional depending on their induction mechanisms. Significance StatementAlzheimers disease (AD) is the most common cause of dementia. Although numerous molecular targets have been identified, the development of treatment is still a challenge. Accumulating evidence shows that artificial control of neuronal activity can modify AD pathology. In particular, the induction of cortical gamma (~40 Hz) oscillations can ameliorate AD pathology and improve cognitive functions. Here we show that optogenetic activation of parvalbumin-positive (PV+) neurons in the basal forebrain (BF) has opposite effects. By expressing channelrhodopsin-2 (ChR2) in PV+ neurons of an AD mouse model and optically stimulating BF PV+ neurons, we induced gamma oscillations and found increased amyloid burden. These results imply that AD pathology can be modified bidirectionally depending on induction mechanisms of gamma oscillations.

neuroscience↗