Informing deep neural networks by multiscale principles of neuromodulatory systems

Flexibly selecting appropriate actions in response to complex, ever-changing environments requires both cortical and subcortical regions, which are typically described as participating in a strict hierarchy. In this traditional view, highly specialized subcortical circuits allow for efficient responses to salient stimuli, at the cost of adaptability and context-specificity, which are attributed to the neocortex. Their interactions are often described as the cortex providing top-down command signals for subcortical structures to implement; however, as available technologies develop, studies increasingly demonstrate that behavior is represented by brain-wide activity and that even subcortical structures contain early signals of choice, suggesting that behavioral functions emerge as a result of different regions interacting as truly collaborative networks. In this review, we discuss the field's evolving understanding of how cortical and subcortical regions in placental mammals interact cooperatively- not only via top-down cortical-subcortical inputs, but through bottom-up interactions, especially via the thalamus. We describe our current understanding of the circuitry of both the cortex and two exemplar subcortical structures- the superior colliculus and striatum- to identify which information is prioritized by which regions. We then describe the functional circuits these regions form with one another- and the thalamus- to create parallel loops and complex networks for brain-wide information flow. Finally, we challenge the classic view that functional modules are contained within specific brain regions; instead, we propose that certain regions prioritize specific types of information over others, but the subnetworks they form- defined by their anatomical connections and functional dynamics- are the basis of true specialization.

Cortical-Subcortical Interactions in Goal-directed Behavior.

https://doi.org/10.1016/j.apsb.2022.11.015

Genomic, transcriptomic, and epigenomic analysis of a medicinal snake, Bungarus multicinctus, to provides insights into the origin of Elapidae neurotoxins

Top-down attention is a dynamic cognitive process that facilitates the detection of the task-relevant stimuli from our complex sensory environment. A neural mechanism capable of deployment under specific task-demand conditions would be crucial to efficiently control attentional processes and improve promote goal-directed attention performance during fluctuating attentional demand. Previous studies have shown that frontal top-down neurons projecting from the anterior cingulate area (ACA) to the visual cortex (VIS; ACAVIS) are required for visual attentional behavior during the 5-choice serial reaction time task (5CSRTT) in mice. However, it is unknown whether the contribution of these projecting neurons is dependent on the extent of task demand. Here, we first examined how behavior outcomes depend on the number of locations for mice to pay attention and touch for successful performance, and found that the 2-choice serial reaction time task (2CSRTT) is less task demanding than the 5CSRTT. We then employed optogenetics to demonstrate that suppression ACAVIS projections immediately before stimulus presentation has no effect during the 2CSRTT in contrast to the impaired performance during the 5CSRTT. These results suggest that ACAVIS projections are necessary when task demand is high, but once a task demand is lowered, ACAVIS neuron activity becomes dispensable to adjust attentional performance. These findings support a model that the frontal-sensory ACAVIS projection regulates visual attention behavior during specific high task demand conditions, pointing to a flexible circuit-based mechanism for promoting attentional behavior.

/pdf/frontal-sensory-cortical-projections-become-dispensable-for-307fr2a7.pdf

Frontal-Sensory Cortical Projections Become Dispensable for Attentional Performance Upon a Reduction of Task Demand in Mice

To obtain more of a particular uncertain reward, animals must learn to actively overcome the lack of reward and adjust behavior to obtain it again. The neural mechanisms underlying such coping with reward omission remain unclear. Here, we developed a task in rats to monitor active behavioral switch toward the next reward after no reward. We found that some dopamine neurons in the ventral tegmental area exhibited increased responses to unexpected reward omission and decreased responses to unexpected reward, following the opposite responses of the well-known dopamine neurons that signal reward prediction error (RPE). The dopamine increase reflected in the nucleus accumbens correlated with behavioral adjustment to actively overcome unexpected no reward. We propose that these responses signal error to actively cope with lack of expected reward. The dopamine error signal thus cooperates with the RPE signal, enabling adaptive and robust pursuit of uncertain reward to ultimately obtain more reward.

https://www.science.org/doi/pdf/10.1126/sciadv.ade5420?download=true

Dopamine error signal to actively cope with lack of expected reward

Post-error recruitment of frontal sensory cortical projections promotes attention in mice.

Cognitive function depends on frontal cortex development; however, the mechanisms driving this process are poorly understood. Here, we identify that dynamic regulation of the nicotinic cholinergic system is a key driver of attentional circuit maturation associated with top-down frontal neurons projecting to visual cortex. The top-down neurons receive robust cholinergic inputs, but their nicotinic tone decreases following adolescence by increasing expression of a nicotinic brake, Lynx1. Lynx1 shifts a balance between local and long-range inputs onto top-down frontal neurons following adolescence and promotes the establishment of attentional behavior in adulthood. This key maturational process is disrupted in a mouse model of fragile X syndrome but was rescued by a suppression of nicotinic tone through the introduction of Lynx1 in top-down projections. Nicotinic signaling may serve as a target to rebalance local/long-range balance and treat cognitive deficits in neurodevelopmental disorders.

https://advances.sciencemag.org/content/advances/7/10/eabe1527.full.pdf

Nicotinic regulation of local and long-range input balance drives top-down attentional circuit maturation

Top-down attention is a dynamic cognitive process that facilitates the detection of the task-relevant stimuli from our complex sensory environment. A neural mechanism capable of deployment under specific task-demand conditions would be crucial to efficiently control attentional processes and improve goal-directed attention performance in task demand-dependent manner. Previous studies have shown that frontal top-down neurons projecting from anterior cingulate area (ACA) to the visual cortex (VIS; ACAVIS) are required for attentional behavior during the 5-choice serial reaction time task (5CSRTT) in mice. However, it is unknown whether the contribution of this projecting neurons is dependent on the extent of task demand. Here, we examine the differential contribution of ACAVIS projection neurons to the attentional behavior in adult male mice performing two visual attention tasks of varying task demand: the 5CSRTT and 2-choice serial reaction time task (2CSRTT). We found that optogenetic suppression ACAVIS projections immediately before stimulus presentation has no effect during the 2CSRTT in contrast to the impaired performance during the 5CSRTT. Fiber photometry calcium imaging of ACAVIS neuron activity revealed that these neurons, which are recruited after errors during 5CSRTT, are not recruited during 2CSRTT. These results suggest that ACAVIS projections are necessary only when task demand is high and that ACAVIS neuron activity may not provide an error monitoring signal when task demand is low. Collectively, this frontal-sensory ACAVIS projection regulates visual attention behavior during specific high task demand conditions, pointing to a flexible circuit-based mechanism for promoting attentional behavior.

https://www.biorxiv.org/content/biorxiv/early/2021/06/26/2021.04.08.439093.full.pdf

Priscilla Maccario

Papers

Post-error recruitment of frontal sensory cortical projections promotes attention in mice.

Nicotinic regulation of local and long-range input balance drives top-down attentional circuit maturation

Task Demand-dependent Contribution of Frontal-Sensory Cortical Projections to Attentional Behavior in Mice