Biology subjects

Mendoza, E.

Publications and source records attributed to Mendoza, E..

6 recordsLinked to original sources

bioRxiv2025

UC Irvine Brain Initiative Cell Atlas Network (BICAN) Brain Procurement Program for the Center for Multiomic Human Brain Cell Atlas Project

High-quality neurotypical postmortem human brain tissue is essential but difficult to obtain for constructing comprehensive human brain cell atlases. Here we describe the establishment of UC Irvines Brain Procurement Program, a coordinated initiative to collect and process neurotypical donor brains for multiomic mapping studies within the NIH BRAIN Initiative Cell Atlas Network (BICAN) consortium. Through partnerships with the Orange County Coroners Office, the UC Irvine Willed Body Program, UCI Medical Center, and the Childrens Hospital of Orange County, we have developed standardized workflows encompassing donor identification, postmortem brain recovery and processing, region-of-interest dissection, neurotypical donor selection, and data management. Our experience demonstrates the feasibility of a community-based, multi-institutional procurement framework while highlighting challenges in recruiting neurotypical donors and ensuring demographic representation reflective of Southern California. We further identify opportunities to strengthen outreach and donation pathways. This program provides a scalable model for advancing population-reflective, high-quality human brain cell atlas efforts. HighlightsO_LIEstablish a multi-site pipeline for procuring high-quality neurotypical human brains. C_LIO_LIDemonstrate feasibility of donor collection across childhood to adulthood. C_LIO_LIIdentify barriers and propose strategies to improve broad donor recruitment. C_LI

neuroscience↗

bioRxiv2024

An improved isochronous pulse after lentiviral knock-down of STEP in Area X of juvenile zebra finches

The zebra finch is one of the most commonly used animal models for studying the genetic mechanisms underlying vocal learning. To investigate the genetic basis of vocal learning, various genes have been knocked down in Area X--a brain region involved in birdsong acquisition--during the critical learning period. All genes that affect speech when mutated in humans similarly impair song learning in zebra finches. To date, no study has demonstrated that not all genes downregulated in Area X result in decreased song learning. Therefore, we sought a candidate gene to knock down in Area X that could either have no effect or potentially improve song learning. STEP is a protein that dephosphorylates many targets in the brain, and its knockout in mice has resulted in enhanced learning. In this study, a lentiviral knockdown of STEP in Area X during song learning resulted in birds producing normal song in almost all parameters and levels of song analysis. This stands in contrast to the knockdown of other genes like all FoxP subfamily members, which resulted in diminished song learning in previous studies. The only parameter positively affected by STEP knockdown was song rhythmicity, as evidenced by a lower deviation of song element onsets from an isochronous pulse than even their tutors. These results demonstrate for the first time that not all knockdowns in Area X lead to deterioration of song learning and validate the specificity of the method and previous findings. Significance StatementThis is the first coding gene knockdown in Area X without negatively affecting song learning.

animal behavior and cognition↗

bioRxiv2024

Characterizing the Spatial Distribution of Dendritic RNA at Single Molecule Resolution

Neurons possess highly polarized morphology that require intricate molecular organization, partly facilitated by RNA localization. By localizing specific mRNA, neurons can modulate synaptic features through local translation and subsequent modification of protein concentrations in response to stimuli. The resulting activity-dependent modifications are essential for synaptic plasticity, and consequently, fundamental for learning and memory. Consequently, high-resolution characterization of the spatial distribution of dendritic transcripts and the spatial relationship across transcripts is critical for understanding the pathways and mechanisms underlying synaptic plasticity. In this study, we characterize the spatial distribution of six previously uncharacterized genes (Adap2, Colec12, Dtx3L, Kif5c, Nsmf, Pde2a) within the dendrites at a sub-micrometer scale, using single-molecule fluorescence in situ hybridization (smFISH). We found that spatial distributions of dendritically localized mRNA depended on both dendrite morphology and gene identity that cannot be recreated by diffusion alone, suggesting involvement of active mechanisms. Furthermore, our analysis reveals that dendritically localized mRNAs are likely co-transported and organized into clusters at larger spatial scales, indicating a more complex organization of mRNA within dendrites.

neuroscience↗

bioRxiv2024

Expression and regulation of SETBP1 in the song system of male zebra finches (Taeniopygia guttata) during singing

Rare de novo heterozygous loss-of-function SETBP1 variants lead to a neurodevelopmental disorder characterized by speech deficits, indicating a potential involvement of SETBP1 in human speech. However, the expression pattern of SETBP1 in brain regions associated with language remains poorly understood, along with the underlying molecular mechanisms linking it to speech. In this study, we examined SETBP1 expression in the brain of male zebra finches, a well-established model for studying vocal production learning. We demonstrated that zebra finch SETBP1 exhibits a greater number of exons and isoforms compared to its human counterpart. We characterized a SETBP1 antibody and showed that SETBP1 colocalized with FoxP1, FoxP2, and Parvalbumin in key song nuclei. Moreover, SETBP1 expression in neurons in Area X is significantly higher in zebra finches singing alone, than those singing courtship song to a female, or non-singers. Importantly, we found a distinctive neuronal protein expression of SETBP1 and FoxP2 in Area X only in zebra finches singing alone, but not in the other conditions. We demonstrated SETBP1s regulatory role on FoxP2 promoter activity in vitro. Taken together, these findings provide compelling evidence for SETBP1 expression in brain regions to be crucial for vocal learning and its modulation by singing behavior.

neuroscience↗

bioRxiv2024

Disinhibition enables vocal repertoire expansion after a critical period

The efficiency of motor skill acquisition is age-dependent, making it increasingly challenging to learn complex maneuvers later in life 1-6. Zebra finches, for instance, acquire a complex vocal motor program during a developmental critical period 7,8 after which the learned song is essentially impervious to modification 9. Although inhibitory interneurons are implicated in critical period closure 10-13, it is unclear whether manipulating them can reopen heightened motor plasticity windows. Using pharmacology and a novel cell-type specific optogenetic approach, we manipulated inhibitory neuron activity in a premotor area of adult zebra finches beyond their critical period. When exposed to auditory stimulation in the form of novel song, manipulated birds added new vocal syllables to their stable song sequence. By lifting inhibition in a premotor area during sensory experience, we reintroduced vocal plasticity, promoting an expansion of the syllable repertoire without compromising pre-existing song production. Our findings provide insights into motor skill learning capacities, offer potential for motor recovery after injury, and suggest avenues for treating neurodevelopmental disorders involving inhibitory dysfunctions.

neuroscience↗

bioRxiv2022

Systems Biology Approach of Understanding Insulin Resistance: Linkage between Type 2 Diabetes and Alzheimer's Disease

Insulin resistance (IR) is a physiological condition in which cells in the body become resistant to insulin. It is a known risk factor associated to type 2 diabetes (T2D). Recently, the idea that IR plays an important role in the progression of Alzheimers disease (AD) has been gaining a lot of attention. Comparing the components of the insulin signalling pathway in relation to T2D and AD, there seems to be a lot of commonality. However, on what role IR plays in linking T2D and AD remains unknown. Through systems biology approach, we extended an existing mathematical model (i.e. ODE based) to study and understand the role IR plays in linking T2D and AD. The simulations, together with the experimental data collected from the literature, show that the common components in T2D and AD express the same dynamical behaviors. This result provides the bases for further modelling of the insulin signaling pathway in determining the link between T2D and AD.

systems biology↗