Research sheds light on cellular basis of depression

Recent studies suggest that neurons in a particular area of the brain called the lateral habenula (LHb) are activated in models of depression. These neurons are activated by stimuli linked to disappointment or anticipation of a negative outcome, and they modulate dopamine-rich regions of the brain that control reward-seeking behavior and play a part in depressive disorders.

Researchers at the University of California, San Diego School of Medicine, along with co-investigators at Cold Spring Harbor Laboratory and Brookhaven National Laboratory, set out to investigate the cellular basis of behavioral depression by studying the synaptic activity of LHb neurons in rats.

Their study, published in the 24 February issue of the journal Nature, showed abnormally strong activity in the neuronal synapses of the LHb in a rat model of depression.  Additionally, when these synapses were inactivated, the animals recovered from the depressive symptoms to some degree.

The research suggests that targeting the specific synapses in this part of the brain could reduce symptoms in humans with severe, chronic depression.

''It's possible that the genes specifically expressed in these neurons could be targeted genetically or pharmacologically in order to manipulate them and reduce depression,'' said Roberto Malinow, MD, PhD, professor of neurosciences at the UCSD School of Medicine and Shiley-Marcos Endowed Chair in Alzheimer's Disease Research, who pointed out that the LHb also has the highest concentration of receptors to opiates.

The scientists utilised widely used animal models of depression called acute learned helplessness (aLH), and a strain of rats with congenital learned helplessness (cLH), produced by selective breeding of animals displaying the greatest amount of aLH.  In both types, the researchers examined transmission to the LHb neurons, which receive major inputs from numerous parts of the brain involved in stress response, as well as those linked to pleasure and pain.