Cerebellar dopamine D2 receptors regulate social behaviors

The cerebellum is a brain area that is best known for its coordination of voluntary movements and error correction capabilities, however, Cutando et. al demonstrate that the cerebellum takes part in cognitive and emotional processes in social interactions as well. The cerebellum’s wide array of capabilities is due to its construction of many independent units, where monoaminergic inputs, like dopamine, deliver inputs about arousal, importance, and the value of stimuli. Tyrosine hydroxylase (TH) is an enzyme that facilitates the reaction that produces L-DOPA, an intermediate to dopamine, norepinephrine, and epinephrine, all of which are catecholamines. Purkinje cells are large neurons with many connections that are unique to the cerebellum. Some of these cells express TH, which allows monoamines to affect neuronal activity.

This study investigated whether changes to the expression of cerebellar dopamine D2 receptors causes motor, cognitive, and social deficits that are observable in autism spectrum disorders, bipolar mood disorder, unipolar depression, posttraumatic stress disorder, or schizophrenia.

The study showed that D2 receptors are assorted throughout the cerebellar cortex but are expressed more in Purkinje cells. It was also demonstrated that these receptors regulate excitatory synaptic signals entering Purkinje cells.

The anatomical and molecular experiments in the cerebellum were done using fully grown male and female mice, but the behavioral experiments were done only with males. Expression of the gene Cre recombinase, which regulates gene expression and reorganizes DNA segments, was induced in the RiboTag strain of mice, who have a modification to their DNA that is activated by Cre. Activating Cre in these mice led to tagging of sites on hemagglutins that bind to receptors on red blood cells, initiating an infection.

The cerebellums were taken from all of the mice groups and examined using several dyes under a microscope. Images were taken of the entire cerebellum. The RNA was then isolated from samples of the cerebellar tissue and a polymerase chain reaction (PCR) was performed.  PCR reveals segments of DNA that can be used to identify a specific trait. Alterations to the Drd2 gene were identified, which is associated with the motor, cognitive, and social deficits in ASD, bipolar mood disorder, depression, PTSD, and schizophrenia, coming from the cerebellum.

In mice that were genetically altered to not express dopamine 2 receptors, their cerebellar motor and cognitive abilities were not damaged, but their social behaviors such as interacting with a stranger mouse or investigating a new environment were decreased. Additionally, blocking dopamine 3 receptor appeared to improve social memory and investigative behaviors. These findings could impact the understanding of inappropriate social interaction in neurological and psychiatric disorders.