A Geometric Approach for the Study of Functional Connectivity Dynamics
Functional connectivity has been the focus of many research groups aiming to study the interaction between cells and brain regions. A standard method for analyzing connectivity is to statistically compare pairwise interactions between cells or brain regions across behavioral states or conditions. This methodology ignores the intrinsic properties of functional connectivity as a multivariate and dynamic signal, expressing the correlational configuration of the network. In this talk, I will present a geometric approach, combining Graph Theory and Riemannian Geometry to build "a graph of graphs" and extract the latent dynamics of the overall correlational structure. Using this approach, we formulate the statistical relations between network dynamics and spontaneous behavior as a second-order Taylor’s expansion. Our analysis shows that fast fluctuations in functional connectivity of large-scale cortical networks are closely linked to variations in behavioral metrics related to the arousal state. We further expand this methodology to longer time scales to study the effect of dopamine on network dynamics in the primary motor cortex (M1) during learning. We developed a series of analysis methods indicating that as animals learn to perform a motor task, the network of pyramidal neurons in layer 2-3 gradually and monotonically reorganizes toward an "expert" configuration. Our results highlight the critical role of dopamine in driving synaptic plasticity: Blocking dopaminergic neurotransmission locally in M1 prevented motor learning at the behavioral level and concomitantly halted plasticity changes in network activity and in functional connectivity. Presented in the van Vreeswijk Theoretical Neuroscience Seminar series (formerly WWTNS) on 2025-01-29. Recording duration: 00:27:08.
Top-down modulation of the retinal code via histaminergic neurons in the hypothalamus
The mammalian retina is considered an autonomous neuronal tissue, yet there is evidence that it receives inputs from the brain in the form of retinopetal axons. A sub-population of these axons was suggested to belong to histaminergic neurons located in the tuberomammillarynucleus (TMN) of the hypothalamus. Using viral injections to the TMN, we identified these retinopetal axons and found that although few in number, they extensively branch to cover a large portion of the retina. Using Ca2+ imaging and electrophysiology, we show that histamine application increases spontaneous firing rates and alters the light responses of a significant portion of retinal ganglion cells (RGCs). Direct activation of the histaminergic axons also induced significant changes in RGCs activity. Since activity in the TMN was shown to correlate with arousal state, our data suggest the retinal code may change with the animal's behavioral state through the release of histamine from TMN histaminergic neurons.
Effects of Vagus Nerve Stimulation on Arousal State and Cortical Excitation
The vagus nerve is a major pathway by which the brain and the body communicate. Electrical stimulation of the vagus nerve (VNS) is widely used as a therapeutic intervention for epilepsy and there is compelling evidence that it can enhance recovery following stroke. Our work demonstrates that VNS exerts a robust excitatory effect on the brain. First, we establish that VNS triggers an increase in arousal state as measured by behavioral state change. This behavioral state change is linked to an increase in excitatory activity within the cortex. We also show that cholinergic and noradrenergic neuromodulatory pathways are activated by VNS, providing a potential mechanism by which VNS may trigger cortical activation. Importantly, the effect of VNS on neuromodulation and cortical excitation persists in anesthetized mice, demonstrating that VNS-induced cortical activation cannot be fully explained by associated behavioral changes.