Quantifying information stored in synaptic connections rather than in firing patterns of neural networks.

A cornerstone of our understanding of both biological and artificial neural networks is that they store information in the strengths of connections among the constituent neurons. However, in contrast to the well-established theory for quantifying information encoded by the firing patterns of neural networks, little is known about quantifying information encoded by its synaptic connections. Here, we develop a theoretical framework using continuous Hopfield networks as an exemplar for associative neural networks, and data that follow mixtures of broadly applicable multivariate log-normal distributions.

Quantifying information stored in synaptic connections rather than in firing patterns of neural networks.

A cornerstone of our understanding of both biological and artificial neural networks is that they store information in the strengths of connections among the constituent neurons. However, in contrast to the well-established theory for quantifying information encoded by the firing patterns of neural networks, little is known about quantifying information encoded by its synaptic connections. Here, we develop a theoretical framework using continuous Hopfield networks as an exemplar for associative neural networks, and data that follow mixtures of broadly applicable multivariate log-normal distributions.

Distinct neural mechanisms construct classical versus extraclassical inhibitory surrounds in an inhibitory nucleus in the midbrain attention network.

Inhibitory neurons in the midbrain spatial attention network, called isthmi pars magnocellularis (Imc), control stimulus selection by the sensorimotor and attentional hub, the optic tectum (OT). Here, we investigate in the barn owl how classical as well as extraclassical (global) inhibitory surrounds of Imc receptive fields (RFs), fundamental units of Imc computational function, are constructed. We find that focal, reversible blockade of GABAergic input onto Imc neurons disconnects their extraclassical inhibitory surrounds, but leaves intact their classical inhibitory surrounds.

Donut-like organization of inhibition underlies categorical neural responses in the midbrain.

Categorical neural responses underlie various forms of selection and decision-making. Such binary-like responses promote robust signaling of the winner in the presence of input ambiguity and neural noise. Here, we show that a 'donut-like' inhibitory mechanism in which each competing option suppresses all options except itself, is highly effective at generating categorical neural responses.

Dynamics of Visual Perceptual Decision-Making in Freely Behaving Mice.

The temporal dynamics of perceptual decisions offer a key window into the cognitive processes contributing to decision-making. Investigating perceptual dynamics in a genetically tractable animal model can facilitate the subsequent unpacking of the underlying neural mechanisms. Here, we investigated the time course as well as fundamental psychophysical constants governing visual perceptual decision-making in freely behaving mice.

Neural Markers of Vulnerability to Anxiety Outcomes after Traumatic Brain Injury.

Anxiety outcomes after traumatic brain injury (TBI) are complex, and the underlying neural mechanisms are poorly understood. Here, we developed a multi-dimensional behavioral profiling approach to investigate anxiety-like outcomes in mice that takes into account individual variability. Departing from the tradition of comparing outcomes in TBI versus sham groups, we identified a subgroup within the TBI group that is vulnerable to anxiety dysfunction, and present increased exploration of the anxiogenic zone compared to sham controls or resilient injured animals, by applying dimensionality reduction, clustering, and validation to behavioral data obtained from multiple assays for anxiety at several post-injury time points.

Mechanisms of competitive selection: A canonical neural circuit framework.

Competitive selection, the transformation of multiple competing sensory inputs and internal states into a unitary choice, is a fundamental component of animal behavior. Selection behaviors have been studied under several intersecting umbrellas including decision-making, action selection, perceptual categorization, and attentional selection. Neural correlates of these behaviors and computational models have been investigated extensively.

Endogenous and exogenous control of visuospatial selective attention in freely behaving mice.

Visuospatial selective attention has been investigated primarily in head-fixed animals and almost exclusively in primates. Here, we develop two human-inspired, discrimination-based behavioral paradigms for studying selective visuospatial attention in freely behaving mice. In the 'spatial probability' task, we find enhanced accuracy, sensitivity, and rate of evidence accumulation at the location with higher probability of target occurrence, and opposite effects at the lower probability location.

Categorical Signaling of the Strongest Stimulus by an Inhibitory Midbrain Nucleus.

The nucleus isthmi pars magnocellularis (Imc), a group of inhibitory neurons in the midbrain tegmentum, is a critical component of the spatial selection network in the vertebrate midbrain. It delivers long-range inhibition among different portions of the space map in the optic tectum (OT), thereby mediating stimulus competition in the OT. Here, we investigate the properties of relative strength-dependent competitive interactions within the Imc, in barn owls of both sexes.

Distinct recruitment of dorsomedial and dorsolateral striatum erodes with extended training.

Hypotheses of striatal orchestration of behavior ascribe distinct functions to striatal subregions, with the dorsolateral striatum (DLS) especially implicated in habitual and skilled performance. Thus neural activity patterns recorded from the DLS, but not the dorsomedial striatum (DMS), should be correlated with habitual and automatized performance. Here, we recorded DMS and DLS neural activity in rats during training in a task promoting habitual lever pressing.

Spatial Dependence of Stimulus Competition in the Avian Nucleus Isthmi Pars Magnocellularis.

The nucleus isthmi pars magnocellularis (Imc) is a group of specialized inhibitory neurons in the midbrain tegmentum, thought to be conserved across vertebrate classes. Past anatomical work in reptiles has suggested a role for it in stimulus selection, which has been supported by recent studies in avians. Additionally, focal inactivation of Imc neurons is known to abolish all competitive interactions in the optic tectum (OT; SC in mammals), a midbrain sensorimotor hub that is critical for the control of spatial attention, thereby revealing a key role for Imc in stimulus selection.

Long-Term Effects of Traumatic Brain Injury on Anxiety-Like Behaviors in Mice: Behavioral and Neural Correlates.

Traumatic brain injury (TBI) has been frequently linked to affective disorders such as anxiety and depression. However, much remains to be understood about the underlying molecular and signaling mechanisms that mediate affective dysfunctions following injury. A lack of consensus in animal studies regarding what the affective sequelae of TBI are has been a major hurdle that has slowed progress, with studies reporting the full range of effects: increase, decrease, and no change in anxiety following injury.

Shank and Zinc Mediate an AMPA Receptor Subunit Switch in Developing Neurons.

During development, pyramidal neurons undergo dynamic regulation of AMPA receptor (AMPAR) subunit composition and density to help drive synaptic plasticity and maturation. These normal developmental changes in AMPARs are particularly vulnerable to risk factors for Autism Spectrum Disorders (ASDs), which include loss or mutations of synaptic proteins and environmental insults, such as dietary zinc deficiency. Here, we show how Shank2 and Shank3 mediate a zinc-dependent regulation of AMPAR function and subunit switch from GluA2-lacking to GluA2-containing AMPARs.

Combinatorial Neural Inhibition for Stimulus Selection across Space.

The ability to select the most salient among competing stimuli is essential for animal behavior and operates no matter which spatial locations stimuli happen to occupy. We provide evidence that the brain employs a combinatorially optimized inhibition strategy for selection across all pairs of stimulus locations. With experiments in a key inhibitory nucleus in the vertebrate midbrain selection network, called isthmi pars magnocellularis (Imc) in owls, we discovered that Imc neurons encode visual space with receptive fields that have multiple excitatory hot spots ("lobes").

Mechanistic target of rapamycin is necessary for changes in dendritic spine morphology associated with long-term potentiation.

Alterations in the strength of excitatory synapses in the hippocampus is believed to serve a vital function in the storage and recall of new information in the mammalian brain. These alterations involve the regulation of both functional and morphological features of dendritic spines, the principal sites of excitatory synaptic contact. New protein synthesis has been implicated extensively in the functional changes observed following long-term potentiation (LTP), and changes to spine morphology have similarly been documented extensively following synaptic potentiation.

Descending control of neural bias and selectivity in a spatial attention network: rules and mechanisms.

The brain integrates stimulus-driven (exogenous) activity with internally generated (endogenous) activity to compute the highest priority stimulus for gaze and attention. Little is known about how this computation is accomplished neurally. We explored the underlying functional logic in a critical component of the spatial attention network, the optic tectum (OT, superior colliculus in mammals), in awake barn owls.

Spatially reciprocal inhibition of inhibition within a stimulus selection network in the avian midbrain.

Reciprocal inhibition between inhibitory projection neurons has been proposed as the most efficient circuit motif to achieve the flexible selection of one stimulus among competing alternatives. However, whether such a motif exists in networks that mediate selection is unclear. Here, we study the connectivity within the nucleus isthmi pars magnocellularis (Imc), a GABAergic nucleus that mediates competitive selection in the midbrain stimulus selection network.

A shared inhibitory circuit for both exogenous and endogenous control of stimulus selection.

The mechanisms by which the brain suppresses distracting stimuli to control the locus of attention are unknown. We found that focal, reversible inactivation of a single inhibitory circuit in the barn owl midbrain tegmentum, the nucleus isthmi pars magnocellularis (Imc), abolished both stimulus-driven (exogenous) and internally driven (endogenous) competitive interactions in the optic tectum (superior colliculus in mammals), which are vital to the selection of a target among distractors in behaving animals. Imc neurons transformed spatially precise multisensory and endogenous input into powerful inhibitory output that suppressed competing representations across the entire tectal space map.

Reciprocal inhibition of inhibition: a circuit motif for flexible categorization in stimulus selection.

As a precursor to the selection of a stimulus for gaze and attention, a midbrain network categorizes stimuli into "strongest" and "others." The categorization tracks flexibly, in real time, the absolute strength of the strongest stimulus. In this study, we take a first-principles approach to computations that are essential for such categorization.

The role of a midbrain network in competitive stimulus selection.

A midbrain network interacts with the well-known frontoparietal forebrain network to select stimuli for gaze and spatial attention. The midbrain network, containing the superior colliculus (SC; optic tectum, OT, in non-mammalian vertebrates) and the isthmic nuclei, helps evaluate the relative priorities of competing stimuli and encodes them in a topographic map of space. Behavioral experiments in monkeys demonstrate an essential contribution of the SC to stimulus selection when the relative priorities of competing stimuli are similar.

Flexible categorization of relative stimulus strength by the optic tectum.

Categorization is the process by which the brain segregates continuously variable stimuli into discrete groups. We report that patterns of neural population activity in the owl optic tectum (OT) categorize stimuli based on their relative strengths into "strongest" versus "other." The category boundary shifts adaptively to track changes in the absolute strength of the strongest stimulus.

Rules of competitive stimulus selection in a cholinergic isthmic nucleus of the owl midbrain.

In a natural scene, multiple stimuli compete for the control of gaze direction and attention. The nucleus isthmi pars parvocellularis (Ipc) is a cholinergic, midbrain nucleus that is reciprocally interconnected to the optic tectum, a structure known to be involved in the control of gaze and attention. Previous research has shown that the responses of many Ipc units to a visual stimulus presented inside the classical receptive field (RF) can be powerfully inhibited when the strength of a distant, competing stimulus becomes the stronger stimulus.

Signaling of the strongest stimulus in the owl optic tectum.

Essential to the selection of the next target for gaze or attention is the ability to compare the strengths of multiple competing stimuli (bottom-up information) and to signal the strongest one. Although the optic tectum (OT) has been causally implicated in stimulus selection, how it computes the strongest stimulus is unknown. Here, we demonstrate that OT neurons in the barn owl systematically encode the relative strengths of simultaneously occurring stimuli independently of sensory modality.

Stimulus-driven competition in a cholinergic midbrain nucleus.

The mechanisms by which the brain selects a particular stimulus as the next target for gaze are poorly understood. A cholinergic nucleus in the owl's midbrain exhibits functional properties that suggest its role in bottom-up stimulus selection. Neurons in the nucleus isthmi pars parvocellularis (Ipc) responded to wide ranges of visual and auditory features, but they were not tuned to particular values of those features.

Global inhibition and stimulus competition in the owl optic tectum.

Stimulus selection for gaze and spatial attention involves competition among stimuli across sensory modalities and across all of space. We demonstrate that such cross-modal, global competition takes place in the intermediate and deep layers of the optic tectum, a structure known to be involved in gaze control and attention. A variety of either visual or auditory stimuli located anywhere outside of a neuron's receptive field (RF) were shown to suppress or completely eliminate responses to a visual stimulus located inside the RF in nitrous oxide sedated owls.