A Signaled Locomotor Avoidance Action Is Fully Represented in the Neural Activity of the Midbrain Tegmentum

Abstract

Animals, including humans, readily learn to avoid harmful and threatening situations by moving in response to cues that predict the threat (e.g., fire alarm, traffic light). During a negatively reinforced sensory-guided locomotor action, known as signaled active avoidance, animals learn to avoid a harmful unconditioned stimulus (US) by moving away when signaled by a harmless conditioned stimulus (CS) that predicts the threat. CaMKII-expressing neurons in the pedunculopontine tegmentum area (PPT) of the midbrain locomotor region have been shown to play a critical role in the expression of this learned behavior, but the activity of these neurons during learned behavior is unknown. Using calcium imaging fiber photometry in freely behaving mice, we show that PPT neurons sharply activate during presentation of the auditory CS that predicts the threat before onset of avoidance movement. PPT neurons activate further during the succeeding CS-driven avoidance movement, or during the faster US-driven escape movement. PPT neuron activation was weak during slow spontaneous movements but correlated sharply with movement speed and, therefore, with the urgency of the behavior. Moreover, using optogenetics, we found that these neurons must discharge during the signaled avoidance interval for naive mice to effectively learn the active avoidance behavior. As an essential hub for signaled active avoidance, neurons in the midbrain tegmentum process the conditioned cue that predicts the threat and discharge sharply relative to the speed or apparent urgency of the avoidance (learned) and escape (innate) responses.

Multimodal convergence in the pedunculopontine tegmental nucleus: motor, sensory and theta-frequency inputs influence activity of single neurons

“…The results of the present study regarding convergence of motor and auditory processing in PPTg strongly support a role in sensorimotor integration. Our findings show that this sensorimotor integration, previously seen in the summed calcium signal from populations of PPTg neurons within (Hormigo et al , 2021), can occur at the single cell level. We found a very high level of convergence of auditory and motor responsiveness, with 81% of reach-related neurons showing tone responses.…”

“…In addition to motor control functions, many PPTg neurons respond strongly at short latency to auditory, visual, vestibular and somatosensory signals (Grunwerg et al , 1992;Reese et al , 1995;Dormont et al , 1998;Ivlieva & Timofeeva, 2003;Carlson et al , 2004;Pan & Hyland, 2005;Aravamuthan & Angelaki, 2012), consistent with a role in sensory processing. Recently, a fiber photometry study has confirmed that the PPTg region generates calcium signal responses to both auditory warning signal, and during the active avoidance locomotion triggered by the cue (Hormigo et al , 2021). While these responses could reflect activity in separate neural channels within PPTg (Pahapill & Lozano, 2000;Tubert et al , 2019), another possibility is that sensory and motor information may converge at the neuronal level allowing for sensorimotor integration in PPTg.…”

Caution Influences Avoidance and Approach Behaviors Differently

“…In a recent paper, we used fiber photometry to compare calcium signals of CaMKII-expressing neurons in the pedunculopontine tegmentum region (PPT) of mice trained in AA1 followed by AA2 (Hormigo et al, 2021a). These neurons show robust activation during performance of signaled active avoidance and are critically required for signaled active avoidance because avoidance is abolished when they are inhibited (Hormigo et al, 2019).…”

Multimodal convergence in the pedunculopontine tegmental nucleus: motor, sensory and theta-frequency inputs influence activity of single neurons

“…In addition to motor control functions, many PPTg neurons respond strongly at short latency to auditory, visual, vestibular and somatosensory signals (Grunwerg et al , 1992;Reese et al , 1995;Dormont et al , 1998;Ivlieva & Timofeeva, 2003;Carlson et al , 2004;Pan & Hyland, 2005;Aravamuthan & Angelaki, 2012), consistent with a role in sensory processing. Recently, a fiber photometry study has confirmed that the PPTg region generates calcium signal responses to both auditory warning signal, and during the active avoidance locomotion triggered by the cue (Hormigo et al , 2021). While these responses could reflect activity in separate neural channels within PPTg (Pahapill & Lozano, 2000;Tubert et al , 2019), another possibility is that sensory and motor information may converge at the neuronal level allowing for sensorimotor integration in PPTg.…”