Type 1 cannabinoid receptors (CB1Rs) are widely expressed in the vertebrate retina but the role of endocannabinoids in vision is not fully understood. Here we identified a novel mechanism underlying a CB1R-mediated increase in retinal ganglion cell (RGC) intrinsic excitability acting through AMPK-dependent inhibition of NKCC1 activity. Clomeleon imaging and patch clamp recordings revealed that inhibition of NKCC1 downstream of CB1R activation reduces intracellular Cl- levels in RGCs, hyperpolarizing the resting membrane potential. We confirmed that such hyperpolarization enhances RGC action potential firing in response to subsequent depolarization, consistent with the increased intrinsic excitability of RGCs observed with CB1R activation. Using a dot avoidance assay in freely swimming Xenopus tadpoles we demonstrate that CB1R activation markedly improves visual contrast sensitivity under low light conditions. These results highlight a role for endocannabinoids in vision, and present a novel mechanism for cannabinoid modulation of neuronal activity through Cl- regulation.
- Jennifer Tsui
- Delphine Gobert
- Edward S Ruthazer
- Edward S Ruthazer
- Loïs S Miraucourt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: This study was performed in strict accordance with the recommendations in the Canadian Council on Animal Care. All animals were handled according to animal care committee protocols (#5071) approved by the Animal Care Committees of the Montreal Neurological Institute and McGill University.
- Gary L Westbrook, Vollum Institute, United States
© 2016, Miraucourt et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
The maintenance of items in working memory (WM) relies on a widespread network of cortical areas and hippocampus where synchronization between electrophysiological recordings reflects functional coupling. We investigated the direction of information flow between auditory cortex and hippocampus while participants heard and then mentally replayed strings of letters in WM by activating their phonological loop. We recorded local field potentials from the hippocampus, reconstructed beamforming sources of scalp EEG, and – additionally in four participants – recorded from subdural cortical electrodes. When analyzing Granger causality, the information flow was from auditory cortex to hippocampus with a peak in the [4 8] Hz range while participants heard the letters. This flow was subsequently reversed during maintenance while participants maintained the letters in memory. The functional interaction between hippocampus and the cortex and the reversal of information flow provide a physiological basis for the encoding of memory items and their active replay during maintenance.
Visually guided behaviors require the brain to transform ambiguous retinal images into object-level spatial representations and implement sensorimotor transformations. These processes are supported by the dorsal 'where' pathway. However, the specific functional contributions of areas along this pathway remain elusive due in part to methodological differences across studies. We previously showed that macaque caudal intraparietal (CIP) area neurons possess robust three-dimensional (3D) visual representations, carry choice- and saccade-related activity, and exhibit experience-dependent sensorimotor associations (Chang et al., 2020b). Here, we used a common experimental design to reveal parallel processing, hierarchical transformations, and the formation of sensorimotor associations along the 'where' pathway by extending the investigation to V3A, a major feedforward input to CIP. Higher-level 3D representations and choice-related activity were more prevalent in CIP than V3A. Both areas contained saccade-related activity that predicted the direction/timing of eye movements. Intriguingly, the time-course of saccade-related activity in CIP aligned with the temporally integrated V3A output. Sensorimotor associations between 3D orientation and saccade direction preferences were stronger in CIP than V3A, and moderated by choice signals in both areas. Together, the results explicate parallel representations, hierarchical transformations, and functional associations of visual and saccade-related signals at a key juncture in the 'where' pathway.