ABSTRACT
There is no consensus on the best inhibitory optogenetic tool. Since Gi/o signalling is a native mechanism of neuronal inhibition, we asked whether Lamprey Parapinopsin ("Lamplight"), a Gi/o-coupled bistable animal opsin, could be used for optogenetic silencing. We show that short (405 nm) and long (525 nm) wavelength pulses repeatedly switch Lamplight between stable signalling active and inactive states, respectively, and that combining these wavelengths can be used to achieve intermediate levels of activity. These properties can be applied to produce switchable neuronal hyperpolarisation and suppression of spontaneous spike firing in the mouse hypothalamic suprachiasmatic nucleus. Expressing Lamplight in (predominantly) ON bipolar cells can photosensitise retinas following advanced photoreceptor degeneration, with 405 and 525 nm stimuli producing responses of opposite sign in the output neurons of the retina. We conclude that bistable animal opsins can co-opt endogenous signalling mechanisms to allow optogenetic inhibition that is scalable, sustained and reversible.
Subject(s)
Opsins , Optogenetics , Animals , Mice , Neurons , Opsins/genetics , Retina , Rod Opsins/geneticsABSTRACT
The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing.
Subject(s)
Circadian Clocks/physiology , Circadian Rhythm/physiology , GABAergic Neurons/metabolism , Suprachiasmatic Nucleus/physiology , Vasoactive Intestinal Peptide/metabolism , Action Potentials/drug effects , Action Potentials/physiology , Animals , Bicuculline/pharmacology , Channelrhodopsins/chemistry , Channelrhodopsins/genetics , Channelrhodopsins/metabolism , Circadian Clocks/drug effects , Corticosterone/blood , Corticosterone/metabolism , Electrodes, Implanted , Female , GABA-A Receptor Antagonists/pharmacology , GABAergic Neurons/drug effects , Heart Rate/physiology , Male , Mice , Mice, Transgenic , Models, Animal , Suprachiasmatic Nucleus/cytology , Vasoactive Intestinal Peptide/antagonists & inhibitors , Vasoactive Intestinal Peptide/geneticsABSTRACT
Endocrine systems function as key mediators of adaptive responses to the external environment. As a reliable predictor of many salient variations in the external world, the light environment thus constitutes an influential source of control over neuroendocrine function. Accordingly, the vast majority of endocrine systems display 24hr variations in activity that are aligned to daily changes in external illumination. While the neural mechanisms responsible for driving these rhythms are still incompletely understood, circadian and light-dependent signals relayed via the suprachiasmatic nucleus of the hypothalamus (SCN) play a key role. Retinal projections to the SCN provide information from rods, cones and melanopsin, which, together, encode variations in the amount and spectral content of ambient light over the solar day. This sensory input, in turn, drives acute modulations in SCN cellular activity and aligns daily rhythms in the electrophysiological output of individual clock neurons. Neural outputs from the SCN can therefore convey both rapid and longer-term information about the light environment to other hypothalamic nuclei responsible for neuroendocrine control. In this review we summarises current understanding of the specific neural pathways by which the light environment influences key neuroendocrine axes, with a particular focus on the retinal and SCN-dependent circuits involved and their known sensory properties.
ABSTRACT
Functional magnetic resonance imaging (fMRI) has increasingly been employed to establish whether there is a specific brain neural network dedicated to maternal responsiveness. We undertook systematic review and meta-analysis of all studies in which healthy new mothers were exposed to visual stimuli of own versus other infants to determine the quality of evidence for a dedicated maternal neural network. Systematic literature review revealed a pattern of specific neural responses commonly induced by visual infant paradigms. Brain areas consistently reported as activated in mothers in response to own versus unknown infant included the left thalamus, bilateral pre-central gyrus, left limbic lobe, uncus, amygdala and left caudate. These regions are implicated in reward, attention, emotion processing and other core social cognitive skills. Meta-analysis, however, revealed a more limited subset of brain areas activated in mothers specifically in response to their own versus unknown infant and suggested considerable inter-study variability. Further work is needed if functional imaging is to become an objective tool for the assessment of neural pathways associated with distinct patterns of maternal care behaviour. Such a tool would be invaluable in developing biomarkers of neural activity associated with healthy maternal care and for monitoring treatment/intervention effects of costly parenting interventions.
