Biology subjects

Tejeda, H.

Publications and source records attributed to Tejeda, H..

6 recordsLinked to original sources

bioRxiv2026

Differential utilization of PACAP and glutamate in parabrachial neurons shapes pain and stress

The external parabrachial nucleus (elPBN) contributes to diverse behaviors, including pain and stress. Neurons in this region use glutamatergic and neuropeptidergic signaling, with pituitary adenylate cyclase-activating polypeptide (PACAP) expressed in a subset of glutamatergic neurons. Deletion of PACAP in elPBN neurons attenuates behavioral responses to stress, but the contribution of PACAP to pain sensitization and of glutamatergic neurotransmission to pain- and stress-related responses remain poorly understood. Here, we show that constitutive loss of PACAP markedly attenuated nerve injury-induced hypersensitivity across heat, pressure, cold and tactile modalities without altering baseline nociception, while also reducing inflammation-induced spontaneous pain-related behavior. Notably, selective deletion of PACAP within elPBN neurons phenocopied the suppression of injury-induced hypersensitivity, but left inflammation- induced pain-related behavior unaffected. Ex vivo optogenetic-assisted circuit mapping showed that activation of PACAP-expressing elPBN terminals elicited glutamatergic transmission onto central amygdala (CeA) PKC{delta}-expressing neurons. Selective deletion of VGluT2 in elPBN neurons reduced nerve injury-induced hypersensitivity but, unlike PACAP deletion, also reduced inflammation-induced pain-related behavior, while leaving stress-induced hypophagia intact. Together, these findings reveal differential requirements for PACAP and glutamatergic neurotransmission within the elPBN across pain- and stress-related behaviors.

neuroscience↗

bioRxiv2025

Hippocampal input-driven plasticity of prefrontal interneurons reveals a circuit basis for impaired spatial working memory.

Long-range projections from ventral hippocampus (vHPC) to medial prefrontal cortex (mPFC) support cognitive functions including spatial working memory (SWM). vHPC input targets multiple prefrontal interneuron classes, yet how hippocampal input recruits these populations in vivo, whether this recruitment is plastic, and how such plasticity influences cognition remain unknown. Here, we combined optical stimulation of mouse vHPC inputs with calcium recordings from discrete mPFC interneuron populations, revealing persistent activity-induced reweighting of hippocampal recruitment across prefrontal inhibitory microcircuits. Ex vivo electrophysiology and computational modeling implicated weakened monosynaptic hippocampal drive onto vasoactive intestinal polypeptide (VIP)-expressing interneurons in this circuit reconfiguration. Prior vHPC input stimulation and the schizophrenia-associated Df(16)A+/- mutation, which also yielded reduced hippocampal input onto VIP interneurons, produced convergent alterations in task-related VIP interneuron activity associated with poorer SWM task learning. These findings implicate hippocampal input to VIP interneurons as a key locus of plasticity capable of reconfiguring inhibitory microcircuit activity linked to impaired working memory task learning. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/665987v2_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@e26cb0org.highwire.dtl.DTLVardef@14d9d6borg.highwire.dtl.DTLVardef@9a0fc2org.highwire.dtl.DTLVardef@80afd1_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO C_FIG

neuroscience↗

bioRxiv2025

Neuropeptidergic transmission shapes emergent properties of prefrontal cortical circuits underlying learning

The prefrontal cortex (PFC) is essential for top-down control of affect and its dysfunction is implicated in many psychiatric disorders. Inhibitory interneurons expressing somatostatin have been implicated in cognition, affect, and disease. However, somatostatins function as a neuropeptide transmitter remains unclear. Here, we investigated the contribution of somatostatin neurotransmission in differentiating between salient (rewarding or aversive) and neutral outcomes. Monitoring somatostatin release and somatostatin receptor antagonism revealed time-dependent regulation of outcome-specific associative learning during acquisition. We found that somatostatin transmission enables configural representations incorporating a salient, aversive outcome in prefrontal cortical neurons, and a threat-driven shift in population-level network activity in-vivo. These findings show a novel role for somatostatin, an interneuron "cellular marker", signaling in shaping learning and emergent network dynamics. Further this framework revealed that reduced somatostatin neuropeptidergic transmission may impair top-down control of affective behaviors observed in mental health disorders, suggesting potential new avenues for therapeutic intervention.

neuroscience↗

bioRxiv2024

Galanin receptor 1 expressing neurons in hippocampal-prefrontal circuitry modulate goal directed attention and impulse control

Neuropeptides like galanin are increasingly recognized as modulators of cognitive pathways. Galanin has been implicated in a wide range of pathological conditions in which frontal and temporal structures are compromised. Recently, we discovered that direct pharmacological stimulation of galanin receptor type 1 (GalR1) in the ventral prefrontal cortex (vPFC) and ventral hippocampus (vHC) caused opposing effects on attention and impulse control behaviors. In the present study, we investigate how neurons expressing GalR1 in these two areas differentially contribute to these behaviors. First, using multiplex fluorescent in situ-hybridization, we established that GalR1 is predominantly expressed in glutamatergic neurons in both the vPFC and vHC. Rats were assessed in their visuospatial attention and impulse control behaviors using the 5- Choice task. We developed a novel viral approach to gain genetic access to GalR1-expressing neurons in the vPFC and vHC, and found that optogenetic excitation of GalR1 expressing neurons in the vPFC, but not vHC, selectively disrupted attention. Finally, using fiber photometry, we measured the bulk calcium dynamics in GalR1-expressing neurons and discovered that GalR1- expressing neurons in the vPFC and vHC showed opposing activity; increased activity in neurons in the vPFC corresponded to correct, attentive actions, whereas activity in the vHC signaled impulsive errors. This region- and response-specific intrinsic activity of galanin, mediated by subclasses of neurons in frontotemporal circuitry participates in shaping the expression of executive-control behaviors that often go awry in various disorders of mental health.

neuroscience↗

bioRxiv2022

Dynorphin / kappa-opioid receptor regulation of excitation-inhibition balance toggles afferent control of prefrontal cortical circuits in a pathway-specific manner.

The medial prefrontal cortex (mPFC) controls emotional behaviors and cognition via connections with limbic excitatory afferents that engage various intra-mPFC inhibitory motifs The mPFC dynorphin (Dyn) / kappa-opioid receptor (KOR) system regulates affect and cognition and is implicated in neuropsychiatric disorders. However, its unclear how neuropeptides in the mPFC, including the Dyn / KOR system, control excitatory and inhibitory circuit motifs integral in information processing. Here, we provide a circuit-based framework wherein selective KOR expression in mPFC afferents or within mPFC feedforward and feedback inhibitory circuits gates how distinct limbic afferent inputs control mPFC neurons. Dyn/KOR signaling directly decreases the ability of KOR-expressing afferent inputs to drive mPFC cell activity. Dyn/KOR signaling also suppresses afferent-driven recruitment of inhibitory sub-networks via several mechanisms, disinhibiting KOR-negative excitatory afferent control of mPFC ensembles. Thus, the Dyn/KOR system toggles which afferent input controls mPFC circuits, providing mechanistic insights into the role of neuropeptides in shaping mPFC function. HighlightO_LIPathway-specific KOR expression confers selective filtering of mPFC afferents by dynorphin C_LIO_LIEndogenous dynorphin release gates KOR-expressing inputs to both dynorphin-expressing and lacking mPFC neurons C_LIO_LIDynorphin / KOR modulation reveals parallel channels within amygdalo-cortical and cortical-cortical circuits C_LIO_LIDynorphin disinhibits mPFC pyramidal neurons via KOR-mediated suppression of distinct inhibitory circuit motifs that preferentially impact SST-mediated feedforward inhibition C_LIO_LIDynorphin / KOR signaling biases afferent control of mPFC principal cells away from KOR-positive and towards KOR-negative afferent inputs C_LI

neuroscience↗

bioRxiv2018

Weakly supervised classification of rare aortic valve malformations using unlabeled cardiac MRI sequences

Biomedical repositories such as the UK Biobank provide increasing access to prospectively collected cardiac imaging, however these data are unlabeled which creates barriers to their use in supervised machine learning. We develop a weakly supervised deep learning model for classification of aortic valve malformations using up to 4,000 unlabeled cardiac MRI sequences. Instead of requiring highly curated training data, weak supervision relies on noisy heuristics defined by domain experts to programmatically generate large-scale, imperfect training labels. For aortic valve classification, models trained with imperfect labels substantially outperform a supervised model trained on hand-labeled MRIs. In an orthogonal validation experiment using health outcomes data, our model identifies individuals with a 1.8-fold increase in risk of a major adverse cardiac event. This work formalizes a learning baseline for aortic valve classification and outlines a general strategy for using weak supervision to train machine learning models using unlabeled medical images at scale.

bioinformatics↗