Dr. Rajan and her lab design neural network models based on experimental data, and reverse-engineer them to figure out how brain circuits function in health and disease. They recently developed a powerful framework for tracing neural paths across multiple brain regions— called Current-Based Decomposition (CURBD). This new approach enables the computation of excitatory and inhibitory input currents that drive a given neuron, aiding in the discovery of how entire populations of neurons behave across multiple interacting brain regions. Dr. Rajan’s team has applied this method to studying the neural underpinnings of behavior. As an example, when CURBD was applied to data gathered from an animal model often used to study depression- and anxiety-like behaviors (i.e., learned helplessness) the underlying biology driving adaptive and maladaptive behaviors in the face of stress was revealed. With this framework Dr. Rajan's team probes for mechanisms at work across brain regions that support both healthy and disease states-- as well as identify key divergences from multiple different nervous systems, including zebrafish, mice, non-human primates, and humans.

Behavior arises from the coordinated activity of numerous distinct brain regions. Modern experimental tools allow access to neural populations brain-wide, yet understanding such large-scale datasets necessitates scalable computational models to extract meaningful features of inter-region communication. In this talk, I will introduce Current-Based Decomposition (CURBD), an approach for inferring multi-region interactions using data-constrained recurrent neural network models. I will first show that CURBD accurately isolates inter-region currents in simulated networks with known dynamics. I will then apply CURBD to understand the brain-wide flow of information leading to behavioral state transitions in larval zebrafish. These examples will establish CURBD as a flexible, scalable framework to infer brain-wide interactions that are inaccessible from experimental measurements alone.

Rajanlab designs neural network models constrained by experimental data, and reverse engineers them to figure out how brain circuits function in health and disease. Recently, we have been developing a powerful new theory-based framework for “in-vivo tract tracing” from multi-regional neural activity collected experimentally. We call this framework CURrent-Based Decomposition (CURBD). CURBD employs recurrent neural networks (RNNs) directly constrained, from the outset, by time series measurements acquired experimentally, such as Ca2+ imaging or electrophysiological data. Once trained, these data-constrained RNNs let us infer matrices quantifying the interactions between all pairs of modeled units. Such model-derived “directed interaction matrices” can then be used to separately compute excitatory and inhibitory input currents that drive a given neuron from all other neurons. Therefore different current sources can be de-mixed – either within the same region or from other regions, potentially brain-wide – which collectively give rise to the population dynamics observed experimentally. Source de-mixed currents obtained through CURBD allow an unprecedented view into multi-region mechanisms inaccessible from measurements alone. We have applied this method successfully to several types of neural data from our experimental collaborators, e.g., zebrafish (Deisseroth lab, Stanford), mice (Harvey lab, Harvard), monkeys (Rudebeck lab, Sinai), and humans (Rutishauser lab, Cedars Sinai), where we have discovered both directed interactions brain wide and inter-area currents during different types of behaviors. With this powerful framework based on data-constrained multi-region RNNs and CURrent Based Decomposition (CURBD), we ask if there are conserved multi-region mechanisms across different species, as well as identify key divergences.

Rajanlab designs neural network models constrained by experimental data, and reverse engineers them to figure out how brain circuits function in health and disease. Recently, we have been developing a powerful new theory-based framework for “in-vivo tract tracing” from multi-regional neural activity collected experimentally. We call this framework CURrent-Based Decomposition (CURBD). CURBD employs recurrent neural networks (RNNs) directly constrained, from the outset, by time series measurements acquired experimentally, such as Ca2+ imaging or electrophysiological data. Once trained, these data-constrained RNNs let us infer matrices quantifying the interactions between all pairs of modeled units. Such model-derived “directed interaction matrices” can then be used to separately compute excitatory and inhibitory input currents that drive a given neuron from all other neurons. Therefore different current sources can be de-mixed – either within the same region or from other regions, potentially brain-wide – which collectively give rise to the population dynamics observed experimentally. Source de-mixed currents obtained through CURBD allow an unprecedented view into multi-region mechanisms inaccessible from measurements alone. We have applied this method successfully to several types of neural data from our experimental collaborators, e.g., zebrafish (Deisseroth lab, Stanford), mice (Harvey lab, Harvard), monkeys (Rudebeck lab, Sinai), and humans (Rutishauser lab, Cedars Sinai), where we have discovered both directed interactions brain wide and inter-area currents during different types of behaviors. With this framework based on data-constrained multi-region RNNs and CURrent Based Decomposition (CURBD), we can ask if there are conserved multi-region mechanisms across different species, as well as identify key divergences.