Rapid, biphasic CRF neuronal responses encode positive and negative valence

Abstract

SUMMARY Corticotropin-releasing factor (CRF) that is released from the paraventricular nucleus (PVN) of the hypothalamus is essential for mediating stress response by activating the hypothalamic-pituitary-adrenal (HPA) axis. CRF-releasing PVN neurons receive inputs from multiple brain regions that convey stressful events, but their neuronal dynamics on the timescale of behavior remain unknown. Here, our recordings of PVN CRF neuronal activity in freely behaving mice revealed that CRF neurons are activated immediately by a range of aversive stimuli. By contrast, CRF neuronal activity starts to drop within a second of exposure to appetitive stimuli. Optogenetic activation or inhibition of PVN CRF neurons was sufficient to induce a conditioned place aversion (CPA) or preference (CPP), respectively. Furthermore, CPA or CPP induced by natural stimuli was significantly decreased by manipulating PVN CRF neuronal activity. Together, these findings suggest that the rapid, biphasic responses of PVN CRF neurons encode the positive and negative valences of stimuli.

Integration of energy homeostasis and stress by parvocellular neurons in rat hypothalamic paraventricular nucleus

“…Despite the apparent neural activation resulting from acute LG treatment in slices, it is also possible that CRH cells were activated even prior to the recordings – by fasting itself, if it is a mild stressor (Kim et al . 2019); such effects could have been overlooked after slice isolation. We carefully tested this possibility in separate experiments, where activation of CRH neurons was estimated in vivo by c‐Fos protein expression.…”

“…An independent in vivo support came recently from Kim et al . (2019), who reported population Ca 2+ responses of CRH neurons both to stressors and appetitive stimuli, regulated at least in part by synaptic inputs to CRH cells. Remarkably, while GABAergic afferents to the PVN appear critical for metabolic responses (Cowley et al .…”

“…1999; Kim et al . 2019). On the background of a mild stress, it is reasonable to expect an elevation in the response to the additional LG stressor because of a simple summation of their effects (Ulrich‐Lai & Herman, 2009).…”

Presynaptic MAST Kinase Controls Bidirectional Post-Synaptic Responses to Convey Stimulus Valence in C. elegans

“…A number of previous studies indicated that the opposing valences of sensory stimuli are encoded by two separate populations of neurons, each of which represents either positive or negative valence of the stimuli 37,38 . By contrast, recent studies proposed an alternative strategy, wherein a single population of neurons responds to appetitive or aversive stimuli and represents the positive or negative valence of the stimuli by increasing or decreasing neuronal activity 39,40 . Specifically, CRF (corticotropin-releasing factor)-releasing neurons in the paraventricular nucleus of the hypothalamus are activated by aversive stimuli and inhibited by appetitive stimuli 40 .…”

“…By contrast, recent studies proposed an alternative strategy, wherein a single population of neurons responds to appetitive or aversive stimuli and represents the positive or negative valence of the stimuli by increasing or decreasing neuronal activity 39,40 . Specifically, CRF (corticotropin-releasing factor)-releasing neurons in the paraventricular nucleus of the hypothalamus are activated by aversive stimuli and inhibited by appetitive stimuli 40 . Likewise, in C. elegans , experience-dependent modulation enables a single set of interneurons to elicit bidirectional responses to carbon dioxide, which can be either attractive or aversive, depending on prior experience 39 .…”