PNB Seminar Series Fall 2026 | Physiology & Neurobiology

September 30, 2026

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Time: 10:30 AM
Location: BPB 130
Host: Karen Menuz

Seminar Title: Leveraging long reads to understand RNA processing in neuronal development

Synopsis

Alternative polyadenylation (APA) is a pervasive co-/post-transcriptional process affecting >70% of human genes, enhancing RNA isoform diversity and regulating mRNA stability, localization, and translation in a spatiotemporal manner. While transcriptome-wide APA analysis in bulk samples has traditionally relied on short-read 3′-end sequencing approaches, these methods lack widespread adoption and resolution of full-length isoforms. Here, we present APALORD (Alternative Polyadenylation Analysis of LOng-ReaDs), a framework for comprehensive APA analysis from long-read (LR) RNA-seq data. Applying APALORD to Oxford Nanopore direct RNA-seq (DRS) data from human embryonic stem cells (hESCs) and hESC-derived neurons, we identify annotated and novel poly(A) sites with high positional accuracy and quantify transcriptome-wide trends in 3′ UTR lengthening during neuronal differentiation. Neurons show increased usage of strong polyadenylation sites enriched for canonical AAUAAA signals, upstream UGUA elements, and downstream GU/U-rich motifs. PAS strength is inversely correlated with the number of sites per gene and positively correlated with gene expression. Extending this approach to developing Drosophila embryos, we identify thousands of novel and highly accurate 3′ end annotations. These results establish APALORD as a powerful tool for dissecting APA regulation at full-length resolution.

October 7, 2026

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Time: 10:30 AM
Location: BPB 130
Host: Anastasios Tzingounis

Seminar Title: KATP channels in metabolic sensing—structural basis of physiology and pathophysiology

Synopsis

KATP channels are unique macromolecular assemblies composed of four pore-forming potassium channel subunits, Kir6.1 or Kir6.2, and four regulatory subunits, SUR1, SUR2A, or SUR2B, which belong to the ABC transporter family. Broadly expressed in many cell types and tissues, KATP channels couple changes in cellular metabolic activity with membrane excitability to control a wide range of physiological processes, from hormone secretion and maintenance of vascular tone to protection of cardiac and neuronal tissues against ischemic injury, as well as learning and memory. Mutations in genes encoding KATP channel subunits are linked to a number of human diseases, including congenital hyperinsulinism, neonatal diabetes, DEND syndrome, and Cantú syndrome. Recent high-resolution KATP cryo-EM structures have revealed complex and dynamic interactions between channel subunits and their ligands. The mechanistic insights provided by these structures offer opportunities to improve KATP pharmacology for diseases caused by channel dysfunction.

October 14, 2026

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Time: 10:30 AM
Location: BPB 130
Host: Scott Rich

Seminar Title: Gating of plasticity by dendritic calcium spikes and its dysregulation in neurodevelopmental disorder

Synopsis

During spatial learning, pyramidal neurons in hippocampal area CA1 rapidly change their selectivity for features of the environment, with a bias towards over-representing goals. Experimental and theoretical evidence suggest that these adaptations reflect a recently discovered form of plasticity induced by dendritic calcium spikes termed behavioral timescale synaptic plasticity (BTSP). Previous work has shown that dendritic calcium spikes are promoted by excitation of distal dendrites by long-range “teaching signals” from cortex, and limited by local dendritic inhibition. Here we investigate the relative contributions of feedback SST+/Chrna2+ (OLM) and feedforward NDNF+ dendrite-targeting interneurons to place field formation and goal over-representation by analyzing data from in vivo calcium imaging experiments performed by our collaborators in the Grienberger lab at Brandeis. Latent factor analysis reveals that OLM and NDNF+ interneuron populations each functionally segregate into multiple subpopulations with distinct profiles of modulation by reward and adaptation over learning. Circuit modeling suggests complementary roles for inhibition from OLM and NDNF+ cells – suppression of OLM interneurons at rewards disinhibits pyramidal cell dendrites and promotes plasticity at reward locations, while enhancement of NDNF+ interneuron activity at rewards provides an additional brake on plasticity that may limit the number of place cells recruited to represent a rewarded location. We have also begun to investigate whether dysregulation of dendritic calcium spiking is a potential mechanism underlying learning impairments in a mouse model of a human genetic neurodevelopmental disorder. I will present data demonstrating that mutation in the G protein subunit Beta1 interferes with activation of inhibitory GIRK channels by GABA(B) receptors in pyramidal cell dendrites, resulting in increased dendritic calcium spiking. These results suggest that modulation of dendritic calcium spiking and BTSP could be a therapeutic target for learning disorders.

November 11, 2026

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Time: 10:30 AM
Location: BPB 130
Host: Natale Sciolino

Seminar Title: Brain, Breath and Body in Stress and Energy Metabolism

Synopsis

Our lab’s research focuses on understanding how brain–body interactions regulate stress-related behavior and energy metabolism. We study these processes through bidirectional brain-to-organ and organ-to-brain pathways. In this work, we investigate the role of the preBötzinger complex, a brainstem region best known as the respiratory rhythm generator, in coordinating behavioral and metabolic responses to stress. Because breathing is tightly linked to autonomic and energetic regulation during stress, we examined PAC1 receptors, which are highly expressed in the preBötzinger complex, as a potential molecular mechanism connecting respiratory control with stress-related fear and metabolism. Our findings indicate that PAC1 signaling in the preBötzinger complex is uniquely positioned to coordinate stress-enhanced fear learning with changes in breathing, heart rate, and whole-body energy metabolism, including alterations in glucose regulation and liver function. Together, these studies support a broader role for the preBötzinger complex as an integrative brainstem hub linking stress, respiration, autonomic physiology, and systemic metabolism.