Spontaneous and sensory-evoked cortical activity is highly state-dependent, promoting the functional flexibility of cortical circuits underlying perception and cognition. Using neural recordings in combination with behavioral state monitoring, we find that arousal and motor activity have complementary roles in regulating local cortical operations, providing dynamic control of sensory encoding. These changes in encoding are linked to altered performance on perceptual tasks. Neuromodulators, such as acetylcholine, may regulate this state-dependent flexibility of cortical network function. We therefore recently developed an approach for dual mesoscopic imaging of acetylcholine release and neural activity across the entire cortical mantle in behaving mice. We find spatiotemporally heterogeneous patterns of cholinergic signaling across the cortex. Transitions between distinct behavioral states reorganize the structure of large-scale cortico-cortical networks and differentially regulate the relationship between cholinergic signals and neural activity. Together, our findings suggest dynamic state-dependent regulation of cortical network operations at the levels of both local and large-scale circuits. Zoom Meeting ID: 964 8138 3003 Contact host if you cannot connect.

Core body temperature is regulated to a setpoint between 36.1 to 37.8°C, with an average fluctuation of 0.5°C during a 24-hour day. Despite mechanistic safeguards, major temperature deviations (1-3°C) from the setpoint occur in the body and in turn the brain. For unknown reasons, in most mammals (humans included), these increases in brain temperature are benign. However, macro-fluctuations in brain temperature in some cases result in deleterious outcomes such as seizures. In this talk, I will describe a mechanism for circuit-level adaptive regulation of cortical activity during macro-fluctuations in brain temperature. I will also discuss how this mechanism can be applied towards the understanding of the pathology of Autism Spectrum Disorder.

We study the dynamics of (inhibitory) balanced networks at varying (i) the level of symmetry in the synaptic connectivity; and (ii) the ariance of the synaptic efficacies (synaptic gain). We find three regimes of activity. For suitably low synaptic gain, regardless of the level of symmetry, there exists a unique stable fixed point. Using a cavity-like approach, we develop a quantitative theory that describes the statistics of the activity in this unique fixed point, and the conditions for its stability. Increasing the synaptic gain, the unique fixed point destabilizes, and the network exhibits chaotic activity for zero or negative levels of symmetry (i.e., random or antisymmetric). Instead, for positive levels of symmetry, there is multi-stability among a large number of marginally stable fixed points. In this regime, ergodicity is broken and the network exhibits non-exponential relaxational dynamics. We discuss the potential relevance of such a “glassy” phase to explain some features of cortical activity.

Spontaneous behavior in animals and humans shows a striking amount of variability both in the spatial domain (which actions to choose) and temporal domain (when to act). Concatenating actions into sequences and behavioral plans reveals the existence of a hierarchy of timescales ranging from hundreds of milliseconds to minutes. How do multiple timescales emerge from neural circuit dynamics? How do circuits modulate temporal responses to flexibly adapt to changing demands? In this talk, we will present recent results from experiments and theory suggesting a new computational mechanism generating the temporal variability underlying naturalistic behavior and cortical activity. We will show how neural activity from premotor areas unfolds through temporal sequences of attractors, which predict the intention to act. These sequences naturally emerge from recurrent cortical networks, where correlated neural variability plays a crucial role in explaining the observed variability in action timing. We will then discuss how reaction times can be accelerated or slowed down via gain modulation, flexibly induced by neuromodulation or perturbations; and how gain modulation may control response timing in the visual cortex. Finally, we will present a new biologically plausible way to generate a reservoir of multiple timescales in cortical circuits.

Spontaneous and sensory-evoked cortical activity is highly state-dependent, promoting the functional flexibility of cortical circuits underlying perception and cognition. Using neural recordings in combination with behavioral state monitoring, we find that arousal and motor activity have complementary roles in regulating local cortical operations, providing dynamic control of sensory encoding. These changes in encoding are linked to altered performance on perceptual tasks. Neuromodulators, such as acetylcholine, may regulate this state-dependent flexibility of cortical network function. We therefore recently developed an approach for dual mesoscopic imaging of acetylcholine release and neural activity across the entire cortical mantle in behaving mice. We find spatiotemporally heterogeneous patterns of cholinergic signaling across the cortex. Transitions between distinct behavioral states reorganize the structure of large-scale cortico-cortical networks and differentially regulate the relationship between cholinergic signals and neural activity. Together, our findings suggest dynamic state-dependent regulation of cortical network operations at the levels of both local and large-scale circuits.

Spontaneous and sensory-evoked cortical activity is highly state-dependent, promoting the functional flexibility of cortical circuits underlying perception and cognition. Using neural recordings in combination with behavioral state monitoring, we find that arousal and motor activity have complementary roles in regulating local cortical operations, providing dynamic control of sensory encoding. These changes in encoding are linked to altered performance on perceptual tasks. Neuromodulators, such as acetylcholine, may regulate this state-dependent flexibility of cortical network function. We therefore recently developed an approach for dual mesoscopic imaging of acetylcholine release and neural activity across the entire cortical mantle in behaving mice. We find spatiotemporally heterogeneous patterns of cholinergic signaling across the cortex. Transitions between distinct behavioral states reorganize the structure of large-scale cortico-cortical networks and differentially regulate the relationship between cholinergic signals and neural activity. Together, our findings suggest dynamic state-dependent regulation of cortical network operations at the levels of both local and large-scale circuits.

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.