Retrograde labeling of oxytocin receptor expressing neurons
Research in the Dölen lab focuses on how the brain enables social behaviors through basic neurobiological processes such as neuromodulation and synaptic plasticity. In addition, we are interested in understanding the pathophysiology of autism and schizophrenia, disorders characterized by profound social and cognitive impairments, with the ultimate goal of designing mechanism-based therapies. Using a combination of well-established, cutting edge, and evolving techniques, our goal is to approach the daunting complexity of the brain armed with molecular, biochemical, optogenetic, electrophysiological, and behavioral strategies to dissect the biological basis of social behavior.
Photo © Jean-Louis Klein & Marie-Luce Hubert
Social behaviors have evolved in species as diverse as colony forming honey bees, schooling tuna fish, pair-bonding penguins, pack wolves, as well as most primates, including humans. For these species, social behaviors are adaptive, yet nevertheless often come at some cost to the individual. Accordingly, it has been suggested that reinforcement of social interactions by the brain’s mesocorticolimbic (MCL) reward system might be required for the evolutionary persistence of these behaviors. While synaptic changes in the MCL reward system have been implicated in drug addiction, relatively little is known about how ethologically relevant “natural” rewards, such as social interaction, are encoded by this circuit. Modern optogenetic technologies afford us the ability to stimulate molecularly isolated input projections independently; when combined with whole-cell patch clamp recording, genetic manipulation, and behavioral assays, we are able to parse the synaptic and circuit elements required for social reward.
Patch clamp electrophysiology and optogenetic input stimulation
Oxytocin (OT) and arginine-vasopressin (AVP) are evolutionarily related peptides which powerfully influence a spectrum of social behaviors including parental care, conjugal and consociate affiliation, aggression, and social recognition across a large diversity of species. These peptides are primarily synthesized and released by discrete populations of cells within the hypothalamus. The Dölen lab is studying the synaptic and circuit effects of these peptides, with a focus on autism relevant functions.
Oxytocin (OT) producing neurons in the hypothalamus
Arginine Vasopressin (AVP) producing neurons in the hypothalamus
‘Autism,’ as first described by Leo Kanner in 1943, is a developmental neuropsychiatric disorder characterized by a profound lack of interest in others. Perhaps the most straightforward hypothesis about how this ‘autistic aloneness’ develops, is that for people with autism, social interactions are simply not rewarding, or, are in some way abnormally rewarding. The Dölen lab focuses on testing this possibility in mouse models of autism. Guided by our mechanistic insights into the synaptic and circuit mechanisms of social reward, we are examining if and how autism genes, when disrupted, lead to aberrant synaptic plasticity, neuromodulation, and neuropeptide regulation across the MCL social reward circuit.
Heider and Simmel, 1944 Johansson, 1973
In addition, we are developing a number of novel behavioral assays that will allow us to screen for autism-relevant social phenotypes in mouse models. For example in humans, the Heider and Simmel task (Heider and Simmel, 1944) is a short animation of two triangles, a circle, and box moving around. Typically developing individuals, but not autistic patients, will attribute thoughts, feelings, and intentions to these shapes. Similarly, point light displays (Johansson, 1973) have been used to determine the minimum amount of information required to perceive biological motion. Although rodent versions of these tasks are not yet available, their development will allow us to test unifying principles common to many causes of autism.