Search bioRxiv⌕ Search

Biology subjects

Jaramillo, J.

Publications and source records attributed to Jaramillo, J..

3 recordsLinked to original sources

Third Trimester-Equivalent Alcohol Exposure Reduces Neurons in Males and Increases Vglut2⁺ Neurons with Reduced Intrinsic Bursting in Females in The Murine Dorsal Subiculum

Individuals with Fetal Alcohol Spectrum Disorders (FASDs) show reduced subicular volume, and preclinical studies compliment this by demonstrating that third-trimester-equivalent ethanol exposure induced apoptosis in corticolimbic regions, including the subiculum. The subiculum mediates hippocampal-cortical communication critical for long-term memory consolidation. Within the distal dorsal subiculum, a population of bursting neurons uniquely express VGLUT2 and they play a key role in memory processing. We hypothesized that third-trimester-equivalent ethanol exposure would reduce neuronal and VGLUT2+ cell density in the dorsal subiculum and reduce the excitability of bursting neurons, providing a mechanism for long-term memory impairments observed in FASD. To test this, postnatal day (P)7 mice received a subcutaneous injection of ethanol and long-term effects were assessed in adolescence (P35-62). Using transgenic mice with fluorescently labeled VGLUT2+ neurons, and immunohistochemistry we observed a significant reduction in neuronal density in males and an increase in VGLUT2+ cell density in females. Using whole-cell patch clamp electrophysiology, we observed a reduction in action potentials per burst in both sexes. Additionally, females showed reduced overall excitability, and a subset of neurons exhibited a shift to regular spiking. These findings suggest that development ethanol exposure disrupts subicular output by impairing burst firing, potentially weaking hippocampal-cortical communication and contributing to the cognitive deficits associated with FASD. HighlightsO_LIThird-trimester ethanol targets VGLUT2+ neurons in the dorsal subiculum C_LIO_LIEthanol reduced neuronal density in male dorsal subiculum C_LIO_LIEthanol increases VGLUT2+ cell density in females C_LIO_LIEthanol reduces action potential per burst in both sexes C_LIO_LIFemales show reduced excitability and loss of bursting in some cells C_LI

neuroscience↗

Predicting distributed working memory activity in a large-scale mouse brain: the importance of the cell type-specific connectome

Recent advances in connectome and neurophysiology make it possible to probe whole-brain mechanisms of cognition and behavior. We developed a large-scale model of the mouse multiregional brain for a cardinal cognitive function called working memory, the brains ability to internally hold and process information without sensory input. The model is built on mesoscopic connectome data for inter-areal cortical connections and endowed with a macroscopic gradient of measured parvalbumin-expressing interneuron density. We found that working memory coding is distributed yet exhibits modularity; the spatial pattern of mnemonic representation is determined by long-range cell type-specific targeting and density of cell classes. Cell type-specific graph measures predict the activity patterns and a core subnetwork for memory maintenance. The model shows numerous self-sustained internal states (each engaging a distinct subset of areas). This work provides a framework to interpret large-scale recordings of brain activity during cognition, while highlighting the need for cell type-specific connectomics.

neuroscience↗

Engagement of pulvino-cortical feedforward and feedback pathways in cognitive computations

Computational modeling of brain mechanisms of cognition has been largely focused on the cortex, but recent experiments have shown that higher-order nuclei of the thalamus, in particular the pulvinar, participate in major cognitive functions and are implicated in psychiatric disorders. Here we show that a pulvino-cortical circuit model, composed of two cortical areas and the pulvinar, captures a range of physiological and behavioral observations related to the macaque pulvinar. Effective connections between the two cortical areas are gated by the pulvinar, allowing the pulvinar to shift the operation regime of these areas during attentional processing and working memory, as well as to resolve decision-making conflict. Furthermore, cortico-pulvinar projections that engage the thalamic reticular nucleus enable the pulvinar to estimate decision-making confidence. Finally, feedforward and feedback pulvino-cortical pathways participate in frequency-dependent inter-areal interactions that modify the relative hierarchical positions of cortical areas. Overall, our model suggests that the pulvinar provides crucial contextual modulation to cortical computations associated with cognition.

neuroscience↗