A Novel Role for the Periaqueductal Gray in Consummatory Behavior

Abstract

The periaqueductal gray (PAG) has a well-established role in pain processing, autonomic function and behavioral responses to fear. Anatomical work suggests the PAG may mediate food intake and reward processing as it has extensive reciprocal connections within brain circuits that mediate appetitive processes and consummatory behaviors such as prefrontal cortex, hypothalamus, amygdala, parabrachial nucleus (PBN) and ventral tegmental area (Kelley et al., 2005). Therefore, we investigated if the PAG of hungry rats has a functional role in appetitive and consummatory behaviors. To address this, PAG was pharmacologically inactivated during a spatial working memory task with muscimol (0.1–0.3 μg), a GABAA agonist via intracranial infusion. Inactivation of PAG led to reduced intake of food rewards and increased errors on this task. To focus on the specific effects PAG inactivation had on food consumption, PAG was inactivated during two separate food intake tasks in a separate group of rats. Again, PAG inactivation resulted in a significant decrease in food consumption, as well as an increased latency to consume food. We next investigated PAG neural responses to reward encounters. A different group of rats performed the same task used in Experiment 1 while the in vivo activity of PAG neurons was recorded. In a subset of PAG neurons, reward encounters elicited phasic excitation. A separate subset of PAG neurons were inhibited during reward encounters. These responses scaled with the size of the reward, with sustained excitation or inhibition in response to large rewards compared to small. Our data also show that separate groups of PAG neurons in awake behaving animals display either increased and decreased neural responses to reward encounters. Additionally, a proportion of neurons were modulated by the animals’ velocity. This study is the first to show that PAG neurons process reward-related information, perhaps to mediate consummatory behaviors related to food consumption.

Mapping heritability of obesity by brain cell types

“…In rats, lesioning of the zona incerta impairs feeding responses 45 while, conversely, in mouse models, optogenetic stimulation of GABAergic neurons in the zona incerta leads to rapid, binge-like eating and body weight gain 46 . Activation of projections from the hypothalamic preoptic nucleus (DEINH5; POA-NEURO21, POA-NEURO66) to the ventral periaqueductal gray (MEGLU2 and MBDOP1) induce object craving 47 , whereas pharmacological inactivation of the periaqueductal gray decreases food consumption 48 . Together, these findings suggest that susceptibility to obesity is enriched in cell types processing sensory stimuli and directing actions related to feeding behavior and opportunity.…”

The lateral periaqueductal gray and its role in controlling predatory hunting and social defense.

“…Behavioral observations have shown that LPAG NMDA lesions interfere with prey hunting; the animals lost their motivation to pursue and attack prey without affecting general levels of arousal, locomotor activity, and regular feeding [22]. In line with these observations, the LPAG contains reward-excited neurons, which exhibited an increased firing rate in response to appetitive food [23]. Conversely, the LPAG has also been shown to respond to a conspecific aggressor.…”

“…By and large, PAG-related responses have been regarded as being mostly stereotyped and dependent on descending projections to the lower brainstem and spinal cord. However, the PAG is also known to influence complex events like approach and avoidance responses to perform risk assessment of potential threats [10][11][12][13], fear memory processing [14][15][16][17][18][19], and reward-seeking [20][21][22][23].…”

The lateral periaqeductal gray and its role in controlling the opposite behavioral choices of predatory hunting and social defense

“…Behavioral observations have shown that LPAG NMDA lesions interfere with prey hunting; the animals lost their motivation to pursue and attack prey without affecting the general levels of arousal, locomotor activity, and regular feeding (Mota-Ortiz et al, 2012). In line with these observations, the LPAG contains reward excited neurons, which exhibited an increased firing rate in response to appetitive food (Tryon and Mizumori, 2018). Conversely, the LPAG has also been shown to respond to a conspecific aggressor.…”

“…However, the PAG is also known to influence complex events like approach and avoidance responses to perform risk assessment of potential threats (Cezario et al, 2008;Sukikara et al, 2010;Souza and Carobrez, 2016;Pobbe et al, 2011), fear memory processing (Deng et al, 2016;Di Scala et al, 1987;Di Scala and Sandner, 1989;Kincheski et al, 2012;Kim et al, 2013;de Andrade Rufino et al, 2019), and reward-seeking (Comoli et al, 2003;Sukikara et al, 2006;Mota-Ortiz et al, 2012;Tryon and Mizumori, 2018).…”