Neuroscience seminars

A fundamental problem in neuroscience is understanding how the properties of individual neurons and synapses contribute to neuronal circuit dynamics and behavior. In recent years we have done both computational and experimental studies that demonstrate that the same physiological output can arise from multiple, degenerate solutions, and that individual animals with similar behavior can nonetheless have quite different sets of underlying circuit parameters. Most recently, we have been studying the resilience of individual animals to perturbations such as temperature and high potassium concentrations. This has revealed that extreme environmental experiences can produce long-term changes in circuit performance that can be hidden, or “cryptic” unless the animals are again challenged or perturbed. Our present experimental and computational work is designed to understand differential resilience in natural, wild-caught animals in response to climate change, and shows long-lasting influences of the animals’ temperature history. VVTNS Fourth Season Closing Lecture. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-06-26. Recording duration: 00:49:33.

Parvalbumin-positive GABAergic interneurons (PV-INs) provide inhibitory control of excitatory neuron activity, coordinate circuit function, and regulate behavior and cognition. PV-INs are uniquely susceptible to loss and dysfunction in traumatic brain injury (TBI) and epilepsy but the cause of this susceptibility is unknown. One hypothesis is that PV-INs use specialized metabolic systems to support their high-frequency action potential firing and that metabolic stress disrupts these systems, leading to their dysfunction and loss. Metabolism-based therapies can restore PV-IN function after injury in preclinical TBI models. Based on these findings, we hypothesize that (1) PV-INs are highly metabolically specialized, (2) these specializations are lost after TBI, and (3) restoring PV-IN metabolic specializations can improve PV-IN function as well as TBI-related outcomes. Using novel single-cell approaches, we can now quantify cell-type-specific metabolism in complex tissues to determine whether PV-IN metabolic dysfunction contributes to the pathophysiology of TBI.

The nervous system orchestrates adaptive behaviors by intricately coordinating responses to internal cues and environmental stimuli. This involves integrating sensory input, managing competing motivational states, and drawing on past experiences to anticipate future outcomes. While traditional models attribute this complexity to interactions between the mesocorticolimbic system and hypothalamic centers, the specific nodes of integration have remained elusive. Recent research, including our own, sheds light on the midline thalamus's overlooked role in this process. We propose that the midline thalamus integrates internal states with memory and emotional signals to guide adaptive behaviors. Our investigations into midline thalamic neuronal circuits have provided crucial insights into the neural mechanisms behind flexibility and adaptability. Understanding these processes is essential for deciphering human behavior and conditions marked by impaired motivation and emotional processing. Our research aims to contribute to this understanding, paving the way for targeted interventions and therapies to address such impairments.

Large-scale recordings of neural activity are providing new opportunities to study network-level dynamics with unprecedented detail. However, the sheer volume of data and its dynamical complexity are major barriers to uncovering and interpreting these dynamics. I will present latent factor analysis via dynamical systems, a sequential autoencoding approach that enables inference of dynamics from neuronal population spiking activity on single trials and millisecond timescales. I will also discuss recent adaptations of the method to uncover dynamics from neural activity recorded via 2P Calcium imaging. Finally, time permitting, I will mention recent efforts to improve the interpretability of deep-learning based dynamical systems models.

Biological systems must selectively encode partial information about the environment, as dictated by the capacity constraints at work in all living organisms. For example, we cannot see every feature of the light field that reaches our eyes; temporal resolution is limited by transmission noise and delays, and spatial resolution is limited by the finite number of photoreceptors and output cells in the retina. Classical efficient coding theory describes how sensory systems can maximize information transmission given such capacity constraints, but it treats all input features equally. Not all inputs are, however, of equal value to the organism. Our work quantifies whether and how the brain selectively encodes stimulus features, specifically predictive features, that are most useful for fast and effective movements. We have shown that efficient predictive computation starts at the earliest stages of the visual system in the retina. We borrow techniques from machine learning, statistical physics, and information theory to assess how we get terrific, predictive vision from these imperfect (lagged and noisy) component parts. In broader terms, we aim to build a more complete theory of efficient encoding in the brain, and along the way have found some intriguing connections between approaches to coarse graining in biology, machine learning, and physics. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2024-06-05. Recording duration: 00:41:40.