Given the intrinsic importance of feeding for survival, one would assume that the brain regions responsible for driving the motivation to obtain food have been thoroughly elucidated. Unlike herbivores, who do not encounter resistance from their food source, carnivores and certain omnivores are faced with the possibility of becoming prey themselves. For animals that rely on consuming other animals for sustenance, the drive to feeding is typically accompanied by instinctual aggression, not only to capture the prey but to kill it before consumption. Moreover, to avoid becoming prey, such animals must possess the ability to anticipate and effectively evade potential dangers. 

Setting aside moral transgressions and ethical violations, the intricate and complex repertoire of human behaviour makes it challenging to parse out the neural circuits that mediate predation and evasion. Fortunately because of phylogenetic continuity between rodents and humans, mice can be used as model organisms to investigate some of these questions. 

To identify the neuronal circuits driving predation in mice, researchers at National Institute of Biological Sciences, Beijing, China, used optogenetic stimulation in inhibitory neurons (neurons expressing the inhibitory neurotransmitter GABA) projecting from the lateral hypothalamus (LH) to the periaqueductal grey (PAG). The LH plays a causal role in predatory aggression, and the PAG is involved in the execution of aggressive behaviour (Haller, 2018; Reis et al., 2023). Activation of LH-originating inhibitory neurons in the PAG was achieved by a combination of transgenic, retrograde tracing, and photostimulation technologies the sum of which enabled the stimulation of LH localized neurons projecting to the PAG.  Limiting the stimulation to GABA-expressing neurons within these two regions, in a cell-type specific manner, meant an increased resolution of this circuit, a feat that a lot of electrical stimulation studies have previously lacked. 

Interestingly, activation of inhibitory LH neurons projecting to the PAG drove strong predatory attack towards prey animals (crickets in this study) as well as other conspecifics, and also towards artificial prey (dummy disk). What is even more intriguing was that the attacks occurred even when the animals were not hungry. This demonstrates the strength of the predation drive elicited by this circuit. Additionally, they found that inhibiting the signal was enough to block predatory attacks. Contrary to inhibitory neurons, activation of excitatory neurons (neurons that express the neurotransmitter glutamate) was observed during evasion. When these excitatory neurons were inhibited, the ability of the animals to anticipate and perform evasive actions was significantly diminished. 

This study is important as it enhances the resolution of the predation drive circuit by specifically focusing on cell-type manipulations, within the LH and PAG, and their effects. As classical electrical stimulation has the disadvantage of activating pass-by axons from other brain regions, the increase in resolution allows a much clearer demarcation of the involvement of different parts of the hypothalamus in eliciting predatory behavior.

Bloggers thoughts: Evidence for the role of the lateral hypothalamus in violent forms of aggression is increasing. However, I would have expected activation of LH excitatory neurons to drive predatory attack in the PAG, rather than inhibitory neurons. As the name suggests, inhibitory neurons inhibit the activity of the region they innervate. It is surprising to me that the inhibition, rather than the activation of the PAG results in predatory attack behavior. Nonetheless, this study helps dissect the predatory drive circuit. I hope the term "predatory drive" sticks, as these authors seemed to have coined it.    

On a more philosophical note, these "behavior at a switch" kinds of studies seem to lend support to the lack of Free Will argument. Technology is becoming increasingly sophisticated. Hypothetically, if such technologies could be used on humans, where one's behavior was controlled by the flip of a switch, what assault would that lend on our current perceptions of autonomy and decision-making? Or would, as usual, people brush it off as inconsequential? Whenever I finish reading one of these kinds of studies, I find myself questioning; are we all but just piano keys, bending to the dictates of physical and biological laws that are outside of our control? If literally turning on a switch is enough to make an animal such as a mouse attack another animal, even an artificial one at that, what would that mean for us, if the technology allowed? Would the behavior be preceded by a decision to attack, or would the decision come later? What would the subjective experience be like in these situations? Think about it. 

Journal Reference:

1. Yi Li, Jiawei Zeng, Juen Zhang, Chenyu Yue, Weixin Zhong, Zhixiang Liu, Qiru Feng, and Minmin Luo*: Hypothalamic Circuits for Predation and Evasion https://doi.org/10.1016/j.neuron.2018.01.005 

References: 

1. Haller, J., 2018. The Role of the Lateral Hypothalamus in Violent Intraspecific Aggression—The Glucocorticoid Deficit Hypothesis. Front Syst Neurosci 12, 26. https://doi.org/10.3389/fnsys.2018.00026

2. Reis, F.M.C.V., Mobbs, D., Canteras, N.S., Adhikari, A., 2023. Orchestration of innate and conditioned defensive actions by the periaqueductal gray. Neuropharmacology 228, 109458. https://doi.org/10.1016/j.neuropharm.2023.10945