When we think of the neurons that control pain-induced behavior, what usually comes to mind are the simple peripheral and spinal reflex circuits described in medical textbooks. This month in Nature Neuroscience (PDF), Caroline Wee, together with collaborators from the Engert, Kunes, Schier, and Douglass (University of Utah) laboratories, reports a neuromodulatory population deep in the zebrafish hypothalamus that is sufficient to drive strong behavioral responses to pain.
These hypothalamic neurons express oxytocin, commonly portrayed as the ‘love’ hormone for its known role in social behaviors. Though oxytocin has also been implicated in mammalian pain processing, it has mainly been studied in the context of pain relief, or the alleviation of fear and anxiety. Nevertheless, there have been some recent and somewhat counterintuitive human studies demonstrating that oxytocin in fact enhances responsiveness to aversive or painful stimuli like electric shock.
Using a combination of brain imaging, behavioral analysis, and circuit manipulation techniques, Wee et. al now show that the zebrafish oxytocin population encodes widespread and diverse sensorimotor representations of noxious stimuli. Further, they find that both the neuropeptide oxytocin and its neurons are capable of driving defensive swimming behavior, by activating a network of brainstem premotor targets. Both the induced behaviors as well as recruited brainstem circuits partially overlap with, but are also distinct from classical predator-escape pathways in zebrafish. Not surprisingly, interfering with oxytocin neuron signaling attenuates pain responses. Taken together with its known functions in mammals, these results emphasize an important and conserved function for oxytocin in pain processing, particularly in the induction of pain-response behaviors.
As Jeremy Bentham once wrote: “Nature has placed mankind under the governance of two sovereign masters, pain and pleasure”. Clearly, even the simple fish brain has evolved strategies to cope with painful stimuli — in the case of these zebrafish, their actions appear to be literally controlled by a hardwired brain circuit that determines what they should do for their own survival. To follow up on these findings, Caroline and colleagues are now investigating how this neuromodulatory circuit interacts with other stimuli, such as food and social cues, to allow for a more flexible control of behavioral output.