January 26, 2016

Circuit tweak enhances social memory in mice

At a Glance

  • Researchers boosted the staying power of social memories in mice by stimulating a specific brain circuit they’d discovered.
  • The study raises the possibility that brain stimulation treatments might someday help patients with declining social memories.
Illustration of neurons Someday, treatments that target particular brain pathways might help people with declining social memories. Svisio/iStock/Thinkstock

Complex social behavior requires social memory—the ability to remember and discriminate between individuals. Formation of social memories depends on a complex interplay of circuits within the brain’s hippocampus that rely on a variety of signaling molecules. Precisely how and where in the hippocampus social memories are formed has been under close study. Understanding this process may lead to treatments for certain types of dementia, amnesia, and cognitive impairment that can seriously strain relationships.

A team at NIH’s National Institute of Mental Health (NIMH) led by Drs. Scott Young and Adam Smith has been studying a region of the hippocampus called CA2. They had previously shown that genetically silencing a receptor expressed in this brain area blocked social memory. The receptor, Avpr1b, reacts with the hormone vasopressin, which is known to play a role in social behavior.

In their latest study, the researchers set out to discover the upstream circuitry that triggers release of vasopressin in the CA2. One candidate was a set of neurons that project to the CA2 from a part of the hypothalamus called the PVN (paraventricular nucleus). The PVN is known to integrate information to orchestrate stress responses. The findings appeared online on January 5, 2016, in the journal Molecular Psychiatry.

The researchers first traced the neurons to confirm a single, anatomically distinct circuit from the PVN that releases vasopressin in the CA2. They then genetically engineered mice so that the circuit responded to pulses of light—a technique called optogenetics. LED optic fibers implanted in the CA2 were used to stimulate the circuit.

Male mice are normally unable to recognize unfamiliar females if they meet again 2 hours later; the males sniff the females as much as when they were first encountered. But when the PVN-CA2 circuit was stimulated while male mice first sniffed out novel females, the males sniffed the females less when reintroduced after periods of at least 7 days afterward. Chemically blocking vasopressin activity in the CA2 prevented this social memory enhancement.

The enhancement worked only if the male’s circuit was stimulated while the memory was being formed, not recalled—and only during its first encounter with a female. The memory remained strong even after the male was distracted by the introduction of a second female mouse, which would normally cause them to forget the first female.

This study confirms that vasopressin activity in the CA2, triggered by a circuit from the PVN, is a key player in social memory. Other pathways are likely involved as well.

“If circuitry similar to what we’re seeing in mice turns out to be also at work in the human brain, treatments based on similar targeted brain pathway stimulation might someday help to improve the relationships of people experiencing social memory impairment due to dementias and mental illnesses,” Young says.

Related Links

References: Targeted activation of the hippocampal CA2 area strongly enhances social memory. Smith AS, Williams Avram SK, Cymerblit-Sabba A, Song J, Young WS. Mol Psychiatry. 2016 Jan 5. doi: 10.1038/mp.2015.189. [Epub ahead of print]. PMID: 26728562.

Funding: NIH’s National Institute of Mental Health (NIMH).