Scientists have found that a brain area other than amygdala could provide more clues into how the brain processes anxiety.
Previous studies of anxiety in the brain have focused on the amygdala, an area known to play a role in fear.
Researchers led by biologists at the California Institute of Technology (Caltech) focused on a different brain area, the lateral septum (LS).
Using mouse models, the team found a neural circuit that connects the LS with other brain structures in a manner that directly influences anxiety.
"Our study has identified a new neural circuit that plays a causal role in promoting anxiety states," said David Anderson, the Seymour Benzer Professor of Biology at Caltech, and corresponding author of the study.
Researchers decided to investigate the so-called septohippocampal axis because previous studies had implicated this circuit in anxiety.
They had also shown that neurons in a structure located within this axis - the LS - lit up, or were activated, when anxious behaviour was induced by stress in mouse models.
Researchers wanted to find out whether the fact that the LS is active in response to stressors mean that this structure promotes anxiety, or whether it means that this structure acts to limit anxiety responses following stress.
In the new study, the team artificially activated a set of specific, genetically identified neurons in the LS of mice. During this activation, the mice became more anxious.
Moreover, the researchers found that even a brief, transient activation of those neurons could produce a state of anxiety lasting for at least half an hour.
This hints that these cells are involved in the initial activation of an anxious state and also that an anxious state persists even after the neurons are no longer being activated.
"The counterintuitive feature of these neurons is that even though activating them causes more anxiety, the neurons are actually inhibitory neurons, meaning that we would expect them to shut off other neurons in the brain," said Anderson.
Researchers then wondered that if these neurons are shutting off other neurons in the brain, then how could they increase anxiety.
The team hypothesised that the process might involve a double-inhibitory mechanism: two negatives make a positive.
Researchers looked at where the LS neurons were making connections in the brain and found they were inhibiting other neurons in a nearby area called the hypothalamus.
Importantly, most of those hypothalamic neurons were, themselves, inhibitory neurons. Moreover, those hypothalamic inhibitory neurons, in turn, connected with a third brain structure called the paraventricular nucleus, or PVN.
The PVN controls release of hormones like cortisol in response to stress and has been implicated in anxiety.
The study was published in the journal Cell.
