Ventral pallidum neurons signal relative threat

Abstract

Ventral pallidum (VP) neurons scale firing increases to reward value and decrease firing to aversive cues.Anatomical connectivity suggests a critical role for the VP in threat-related behavior. Here we tested whether firing decreases in VP neurons conform to relative threat by recording single units while male rats discriminated cues predicting unique foot shock probabilities. Rats behavior and VP single unit firing discriminated danger, uncertainty and safety cues. We found that two VP populations (Low firing and Intermediate firing) signaled relative threat, proportionally decreased firing according shock probability: danger < uncertainty < safety. Low firing neurons showed reward firing increases, consistent with a general signal for relative value.Intermediate firing neurons were unresponsive to reward, revealing a specific signal for relative threat. The results suggest an integral role for the VP in threat-related behavior. ResultsMale, Long Evans rats (n = 14) were moderately food-deprived and trained to nose poke in a central port in order to receive a reward (food pellet). Nose poking was reinforced throughout fear discrimination, but poke-reward and cue-shock contingencies were independent. During fear discrimination, three distinct auditory cues predicted unique foot shock probabilities: danger (p=1.00), uncertainty (p=0.25), and safety (p=0.00) (Fig. 1a). Each fear discrimination session consisted of 16 trials: 4 danger, 2 uncertainty-shock, 6 uncertainty-omission, and 4 safety, mean 3.5 min inter-trial interval (ITI). Each trial started with a 20 s baseline period followed by 10 s cue presentation. Foot shock (0.5 mA, 0.5 s) was administered 2 s following cue offset on shock trials (Fig. 1b). Trial order was randomized for each rat, each session. Fear was measured by the suppression of rewarded nose poking. A suppression ratio was calculated by comparing nose poke rates during baseline and cue periods (see methods). After eight discrimination sessions, rats were implanted with drivable microelectrode bundles dorsal to the VP (Fig. 1c). Following recovery, single unit activity was recorded while rats underwent fear discrimination. The microelectrode bundle was advanced through

Retrorubral field is a hub for diverse threat and aversive outcome signals

“…29 RRF neurons categorizing cues into danger, uncertainty, and threat may project to brain regions that do not elicit fear de novo but shape adaptive fear responses, such as the nucleus accumbens 30 and ventral pallidum. 32 Yet function-projection relationships will likely defy simplicity. Neurons fully differentiating cues showed divergent firing patterns following aversive outcome, ranging from positive prediction error signaling to sustained threat and valence signaling.…”

“…In our discrimination procedure, rats typically show a pattern of fear that is intermediate to the extremes that would be produced by only RRF or only vlPAG neurons. Threat predictions arising in the amygdala, 79 prefrontal cortices, 41,80,81 ventral pallidum, 32 nucleus accumbens, 30 and additional brain regions 10 S4. Article likely interact with one another.…”

“…27,28 The RRF is anatomically poised to interact with a larger threat network. RRF neurons, including A8 dopamine, directly project to regions essential to fear, including medullary/pontine regions, 29 the central amygdala, 1,3 nucleus accumbens core, 30,31 ventral pallidum, 32,33 bed nucleus of the stria terminalis, 34,35 and hippocampus. 36,37 Indeed, RRF neuron-type composition and connectivity have led to previous proposals for a role in fear.…”

Distinct threat and valence signals in rat nucleus accumbens core

“…The recording/fear discrimination approach is based on prior work from our laboratory (Moaddab et al, 2021).…”

“…While the amygdala is undoubtedly important, threat learning and behavior is normally the product of a much larger network (Beck and Fibiger, 1995; Vetere et al, 2017). This network includes traditional ‘reward’ regions (Reynolds and Berridge, 2002; Pauli et al, 2015; Bouchet et al, 2018; Groessl et al, 2018; Cai et al, 2020; Piantadosi et al, 2020; Stephenson-Jones et al, 2020; Moaddab and McDannald, 2021; Moaddab et al, 2021). The NAcc receives a prominent, direct projection from the basolateral amygdala (Christie et al, 1987; Brog et al, 1993; Li et al, 2018).…”