Biology subjects

Vasquez, B.

Publications and source records attributed to Vasquez, B..

5 recordsLinked to original sources

bioRxiv2025

AI for IACUC: Accurate Initial Assessment of Institutional Animal Care and Use Committee Protocols

Every animal protocol requires careful review to ensure humane principles, laws, and policies are followed before any experiments may be performed. Developing protocols and receiving approval can be a lengthy process requiring multiple rounds of feedback and refinement. Artificial Intelligence (AI) has the potential to improve the quality and speed of IACUC protocol reviews by detecting submission errors. We describe an approach to achieve this and show that our approach can be replicated, while addressing issues of ethics and bias, robustness, and trustworthiness1. Replication is addressed by developing a template and demonstrating that it can be reused. Ethics and bias issues are addressed by early, limited use of a large language Model (LLM) to identify errors and rapidly provide useful feedback to the protocol developer. In our approach, subsequent steps still require a review by the IACUC board, which retains ethical responsibility for approval. Robustness and trustworthiness were evaluated by using the template that is replicated for eleven distinct checks and performed on 50 new protocols using two different LLMs. We show that every actual problem in those submissions (within the test parameters) is found by our AI review (i.e., recall=100%), giving IACUC boards confidence in the utility of our system. In addition, precision for our checks is between 80%-100%, with most being 100%, thereby making the system a practical compliment to administrative protocol review for those submitting. Overall, we report F1 scores of between 89-100%.

scientific communication and education↗

bioRxiv2025

Post-Ictal Gamma Oscillations Predict Hippocampal Structural Integrity in Mesial Temporal Lobe Epilepsy

The underlying histopathology and epileptic network of patients with mesial temporal lobe epilepsy (mTLE) are difficult to ascertain. Here, we report a novel electrical activity following seizure termination, termed post-ictal gamma oscillations (PIGOs), recorded in mice with intrahippocampal kainic acid injection and a patient with mTLE. PIGOs are characterized by a spectral shift of increased power in gamma frequencies relative to decreased power in other frequencies, generating a gamma peak. PIGOs are accompanied by increased intracellular calcium levels among parvalbumin-positive interneurons and a direct current shift. Only a subgroup of animals in the study had PIGOs. These animals had less pronounced hippocampal sclerosis (HS) than those without PIGOs. To illustrate the translational potential of these findings, we analyzed data from two patients with unilateral mTLE, one with PIGOs and the other without. The patient with PIGOs had symmetrical hippocampi on neuroimaging, whereas the other exhibited overly decreased interictal glucose uptake in left hippocampus, suggesting left-sided HS. After receiving laser ablation of mesial temporal regions, the patient with PIGOs became seizure-free, whereas the other did not. Our results suggest that PIGOs may serve as a biomarker for a milder form of HS in patients with mTLE and for predicting treatment outcomes.

neuroscience↗

bioRxiv2022

High sensitivity intrinsic optical signal imaging through flexible, low-cost adaptations of an upright microscope

Intrinsic optical signal imaging (IOSI) is a staple technique in modern neuroscience. Pioneered over thirty years ago, IOSI allows macroscopic mapping of neuronal activity throughout the cortex. The technique has been used to study sensory processing and experience-dependent plasticity, and is often used as an adjunctive procedure to localize cortical areas for subsequent targeting by other imaging or physiology techniques. Despite the ubiquity of IOSI in neuroscience there are few commercially available IOSI systems. As a result, investigators have typically resorted to building their own imaging systems. Over the years, simplified systems built on existing microscope platforms have been proposed. Still, these often require additional, sometimes costly, custom-built hardware, which presents challenges for investigators without significant experience in optics or microscopy design. Here we present a straightforward set of adaptations that can be applied to any standard upright microscope, using readily available, inexpensive, commercial parts for illumination, optics, and signal detection, that enables high sensitivity IOSI. Using these adaptations, we are able to readily map sensory-evoked signals across the somatosensory and visual cortex, including single-whisker barrel cortical activity maps in mice. We show that these IOSI maps are highly reproducible across animals and can be used to study plasticity mechanisms in the somatosensory cortex. We also provide open-source applications to control illumination and analyze raw data to generate activity maps. We anticipate these resources will be particularly useful for neuroscience investigators from broad technical backgrounds looking to add IOSI capabilities to an existing microscope on a budget.

neuroscience↗

bioRxiv2022

Activation of the CA2-vCA1 pathway reverses social discrimination dysfunction in Shank3B knockout mice

Social memory dysfunction is a feature of several neuropsychiatric and neurodevelopmental disorders. Mutation or deletion of the SHANK3 gene, which codes for a synaptic scaffolding protein, has been linked to autism spectrum disorder (ASD) and Phelan-McDermid syndrome, conditions associated with impairments in social memory. Shank3B knockout (KO) mice exhibit several behavioral abnormalities that may be analogous to symptoms of ASD, including social discrimination deficits. The CA2 region of the hippocampus integrates numerous afferents and sends a major output to the ventral CA1 (vCA1), circuitry that plays an important role in social memory. Despite finding few differences in excitatory afferents to the CA2 in Shank3B KO mice, chemogenetic activation of CA2 excitatory neurons restored social recognition function to wildtype (WT) levels. Specific activation of the CA2-vCA1 circuitry had a similar effect. Neuronal oscillations in the theta, gamma and, sharp wave ripple ranges have been linked to social memory, but we observed no differences in these measures between WT and Shank3B KO mice in the vCA1 in response to social stimuli. However, activation of CA2 excitatory neurons enhanced vCA1 theta power in Shank3B KO mice, concurrent with behavioral improvements. These findings suggest that stimulating adult circuitry in a mouse model with neurodevelopmental impairments can be sufficient to invoke latent function, particularly with respect to social memory dysfunction. The extent to which vCA1 network oscillations in the theta range are responsible for rescued behavioral function remains unknown.

neuroscience↗

bioRxiv2022

The estrous cycle modulates early-life adversity effects on mouse avoidance behavior through progesterone signaling

Early-life adversity (ELA) predisposes individuals to develop neuropsychiatric conditions, which are more prevalent in women than men. Efforts to model this sex difference in rodents have produced mixed results, with some studies paradoxically showing stronger phenotypes in males than females. Since changes in reproductive hormone levels can increase the likelihood of anxiety disorders in women, we examined the effects of ELA on adult female mice across the estrous cycle. We found that during diestrus, when the ratio of progesterone to estrogen is relatively high, ELA mice exhibit increased avoidance behavior, altered activity levels in specific contexts, and increased theta oscillation power in the ventral hippocampus. Ovariectomy, which eliminates circulating estrogen but not progesterone, unexpectedly preserved some of the effects present in diestrus ELA mice. Progesterone receptor antagonism in diestrus normalized avoidance behavior in ELA mice, while treatment with a negative allosteric modulator of the progesterone metabolite allopregnanolone promoted avoidance behavior in control mice. These results suggest that altered progesterone and allopregnanolone signaling during diestrus increases avoidance behavior in ELA mice

neuroscience↗