While it is generally accepted that neurons control complex behavior and brain computation, the role of non-neuronal cells in this context remains unclear. Astrocytes, glial cells of the central nervous system, exhibit complex forms of chemical excitation, most prominently calcium transients, evoked by local and projection neuron activity. In this talk, I will provide mechanistic links between astrocytes’ spatiotemporally complex activity patterns, neuronal molecular signaling, and behavior. Using a visual detection task, in vivo calcium imaging, robust statistical analyses, and machine learning approaches, my work shows that cortical astrocytes encode the animal's decision, reward, performance level, and sensory properties. Behavioral context and motor activity-related parameters strongly impact astrocyte responses. Error analysis confirms that astrocytes carry behaviorally relevant information, supporting astrocytes' complementary role to neuronal coding beyond their established homeostatic and metabolic roles.

Mammalian vision and visually-guided behavior relies on neurons distributed across diverse brain regions. In this talk I will describe our efforts to create tools that allow us to measure activity from these distributed circuits - Neuropixels probes for large-scale electrophysiology - and our findings from studies deploying these tools to study visual detection and discrimination in mice.

Neural and behavioral responses to sensory stimuli are notoriously variable from trial to trial. Does this mean the brain is inherently noisy or that we don’t completely understand the nature of the brain and behavior? Here we monitor the state of activity of the animal through videography of the face, including pupil and whisker movements, as well as walking, while also monitoring the ability of the animal to perform a difficult auditory or visual task. We find that the state of the animal is continuously changing and is never stable. The animal is constantly becoming more or less activated (aroused) on a second and subsecond scale. These changes in state are reflected in all of the neural systems we have measured, including cortical, thalamic, and neuromodulatory activity. Rapid changes in cortical activity are highly correlated with changes in neural responses to sensory stimuli and the ability of the animal to perform auditory or visual detection tasks. On the intracellular level, these changes in forebrain activity are associated with large changes in neuronal membrane potential and the nature of network activity (e.g. from slow rhythm generation to sustained activation and depolarization). Monitoring cholinergic and noradrenergic axonal activity reveals widespread correlations across the cortex. However, we suggest that a significant component of these rapid state changes arise from glutamatergic pathways (e.g. corticocortical or thalamocortical), owing to their rapidity. Understanding the neural mechanisms of state-dependent variations in brain and behavior promises to significantly “denoise” our understanding of the brain.