In the retina, photoreceptors pass visual information to interneurons, which process it and pass it to retinal ganglion cells (RGCs). Axons of RGCs then travel through the optic nerve, telling the rest of the brain all it will ever know about the visual world. Research over the past several decades has made clear that most RGCs are not merely light detectors, but rather feature detectors, which send a diverse set of parallel, highly processed images of the world on to higher centers. Here, we review progress in classification of RGCs by physiological, morphological, and molecular criteria, making a particular effort to distinguish those cell types that are definitive from those for which information is partial. We focus on the mouse, in which molecular and genetic methods are most advanced. We argue that there are around 30 RGC types and that we can now account for well over half of all RGCs. We also use RGCs to examine the general problem of neuronal classification, arguing that insights and methods from...

The types of retinal ganglion cells: current status and implications for neuronal classification.

The thalamus is crucial in determining the sensory information conveyed to cortex. In the visual system, the thalamic lateral geniculate nucleus (LGN) is generally thought to encode simple center-surround receptive fields, which are combined into more sophisticated features in cortex, such as orientation and direction selectivity. However, recent evidence suggests that a more diverse set of retinal ganglion cells projects to the LGN. We therefore used multisite extracellular recordings to define the repertoire of visual features represented in the LGN of mouse, an emerging model for visual processing. In addition to center-surround cells, we discovered a substantial population with more selective coding properties, including direction and orientation selectivity, as well as neurons that signal absence of contrast in a visual scene. The direction and orientation selective neurons were enriched in regions that match the termination zones of direction selective ganglion cells from the retina, suggesting a source for their tuning. Together, these data demonstrate that the mouse LGN contains a far more elaborate representation of the visual scene than current models posit. These findings should therefore have a significant impact on our understanding of the computations performed in mouse visual cortex.

https://www.jneurosci.org/content/jneuro/33/11/4642.full.pdf

Diverse Visual Features Encoded in Mouse Lateral Geniculate Nucleus

Predictions about future rewarding events have a powerful influence on behaviour. The phasic spike activity of dopamine-containing neurons, and corresponding dopamine transients in the striatum, are thought to underlie these predictions, encoding positive and negative reward prediction errors. However, many behaviours are directed towards distant goals, for which transient signals may fail to provide sustained drive. Here we report an extended mode of reward-predictive dopamine signalling in the striatum that emerged as rats moved towards distant goals. These dopamine signals, which were detected with fast-scan cyclic voltammetry (FSCV), gradually increased or--in rare instances--decreased as the animals navigated mazes to reach remote rewards, rather than having phasic or steady tonic profiles. These dopamine increases (ramps) scaled flexibly with both the distance and size of the rewards. During learning, these dopamine signals showed spatial preferences for goals in different locations and readily changed in magnitude to reflect changing values of the distant rewards. Such prolonged dopamine signalling could provide sustained motivational drive, a control mechanism that may be important for normal behaviour and that can be impaired in a range of neurologic and neuropsychiatric disorders.

Prolonged dopamine signalling in striatum signals proximity and value of distant rewards

Cortical neurons in thalamic recipient layers receive excitation from the thalamus and the cortex. The relative contribution of these two sources of excitation to sensory tuning is poorly understood. We optogenetically silenced the visual cortex of mice to isolate thalamic excitation onto layer 4 neurons during visual stimulation. Thalamic excitation contributed to a third of the total excitation and was organized in spatially offset, yet overlapping, ON and OFF receptive fields. This receptive field structure predicted the orientation tuning of thalamic excitation. Finally, both thalamic and total excitation were similarly tuned to orientation and direction and had the same temporal phase relationship to the visual stimulus. Our results indicate that tuning of thalamic excitation is unlikely to be imparted by direction- or orientation-selective thalamic neurons and that a principal role of cortical circuits is to amplify tuned thalamic excitation.

https://escholarship.org/content/qt4xs9g7zc/qt4xs9g7zc.pdf?t=qam67p

Tuned thalamic excitation is amplified by visual cortical circuits

Sensory perception depends on the context in which a stimulus occurs. Prevailing models emphasize cortical feedback as the source of contextual modulation. However, higher order thalamic nuclei, such as the pulvinar, interconnect with many cortical and subcortical areas, suggesting a role for the thalamus in providing sensory and behavioral context. Yet the nature of the signals conveyed to cortex by higher order thalamus remains poorly understood. Here we use axonal calcium imaging to measure information provided to visual cortex by the pulvinar equivalent in mice, the lateral posterior nucleus (LP), as well as the dorsolateral geniculate nucleus (dLGN). We found that dLGN conveys retinotopically precise visual signals, while LP provides distributed information from the visual scene. Both LP and dLGN projections carry locomotion signals. However, while dLGN inputs often respond to positive combinations of running and visual flow speed, LP signals discrepancies between self-generated and external visual motion. This higher order thalamic nucleus therefore conveys diverse contextual signals that inform visual cortex about visual scene changes not predicted by the animal's own actions.

/pdf/thalamic-nuclei-convey-diverse-contextual-information-to-3hur4b2jf6.pdf

Thalamic nuclei convey diverse contextual information to layer 1 of visual cortex.

Anterior-Posterior Direction Opponency in the Superficial Mouse Lateral Geniculate Nucleus

The Habenula: Darkness, Disappointment, and Depression.

Predictive coding emerged as an explanation for how the brain can efficiently encode sensory stimuli. The hierarchical organization of neural circuits for perception thus passes prediction errors between computational layers. Extensions of this theory have provided a unifying understanding of Bayesian inference within neural circuits and psychiatric disorders. In particular, disorders of perception and belief have been explained as a Bayesian process of weighing prior beliefs (predictions) against new sensory data (prediction errors). The present issue of the Journal of Abnormal Psychology provides further evidence for how psychotic disorders develop and persist and how addiction- and trauma-related disorders may also be conceptualized. Trauma-related disorders in particular have begun to be identified as disorders of excessive accumulated prediction errors (uncertainty) over life. Here we summarize and reconcile recent advances in reinforcement learning momentum models with predictive processing and attempt to point out potential pitfalls for the application of hierarchical prediction models to stress. Future directions for understanding stress through this lens may need to involve updates to a purely hierarchical view or reframing long times cale molecular predictions as higher-order predictions. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Predictive processing in mental illness: Hierarchical circuitry for perception and trauma.

Illness anxiety disorder (IAD, formerly hypochondriasis) is characterized by preoccupation with fear of serious illness despite medical reassurance. IAD is common, debilitating, challenging to treat, and results in high healthcare utilization. Outpatient management of IAD is challenging because patients can compulsively seek reassurance from numerous providers, which interferes with learning more productive coping skills. We present the case of a woman with severe IAD who presented to the emergency room with increasing frequency over several months, despite regular outpatient medical visits and escalating psychiatric care. We made the unusual decision to hospitalize her for IAD for 1 month, in the absence of typical hospitalization criteria. This hospitalization allowed us to consolidate all medical and psychiatric care into a single provider team and train all staff and family to communicate with her in a consistent manner. We successfully treated her by integrating a general cognitive-behavioral therapy (CBT) protocol into medical care and decision-making. In response to her numerous health concerns, we minimized medical work-up, reassurance, and reactive medication changes, and instead used the concerns as opportunities to reinforce the psychotherapy. This approach allowed us to simplify her medication regimen and manage her co-morbid hypertension and vitamin deficiencies. Though inpatient hospitalization is likely infeasible in most cases of IAD, outpatient providers may create similar treatment plans based on the example of our case report, without needing highly specialized expertise. Such a plan would require a straightforward understanding of IAD psychology, which we review here, combined with readily accessible tools including a universal CBT protocol, online CBT courses, and clinical symptom scales. We discuss our approach for responding to health concerns, maintaining therapeutic alliance, integrating CBT principles into patient interactions, and managing medications. Since patients with IAD share health concerns with all providers, staff, and family, we also include our own IAD communication guide, appropriate for a general audience, that demonstrates how to respond in these conversations.

/pdf/severe-illness-anxiety-treated-by-integrating-inpatient-283vrqgso2.pdf

Alfred P. Kaye

Papers

Anterior-Posterior Direction Opponency in the Superficial Mouse Lateral Geniculate Nucleus

The Habenula: Darkness, Disappointment, and Depression.

Predictive processing in mental illness: Hierarchical circuitry for perception and trauma.

Severe Illness Anxiety Treated by Integrating Inpatient Psychotherapy With Medical Care and Minimizing Reassurance

Transcriptomics of the depressed and PTSD brain.