April 24, 2014. Cognition is thought to rely on the coordinated firing of neurons, but exactly how this works has been difficult to establish. A new study published April 24 in Cell gets a bit more specific about this relationship in mice: Susumu Tonegawa and colleagues at the Massachusetts Institute of Technology in Boston report increases in synchronized high-frequency neural oscillations between the entorhinal cortex (EC) and hippocampus just prior to making a correct choice in a working memory task. The results suggest that this transient increase in synchrony reflects the transfer of information out of working memory for use in a task.
The new link may hold some relevance for schizophrenia, which is characterized by deficits in working memory and alterations in gamma oscillations. Working memory is the brain’s temporary holding tank for information that needs to be stored and manipulated to execute a task. People with schizophrenia seem unable to hold as many things in working memory as healthy controls can (see SRF related news report), and this could compromise many other aspects of cognition. Likewise, alterations in neural oscillations, including those in the gamma range (25-140 Hz), are found in schizophrenia under certain conditions (e.g., see Abstract) and in rodent models of schizophrenia (see SRF related news report).
In the new study, first author Jun Yamamoto and colleagues tracked oscillations in the EC and hippocampus simultaneously in mice as they moved through a T-shaped maze. In a “sample” trial, one arm of the maze was open and contained a food reward. In the next “test” trial, both arms were open, and the mice had to remember which arm the reward had been in, then go into the opposite arm. The researchers found a transient uptick in synchrony between the high-frequency gamma range (65-140 Hz) oscillations emanating from the EC and the hippocampus just before mice made a correct choice. This also appeared in “oops” trials, when mice began to enter the wrong arm but then reversed course to go into the correct one. In contrast, increased synchrony did not emerge when mice made incorrect choices.
Severing a connection between the EC and the hippocampus disrupted working memory: Specifically, optogenetically silencing EC neurons projecting to the CA1 layer of the hippocampus just as mice approached the T-junction where they needed to make a choice decreased both synchrony and the percentage of correct trials. This may have interrupted the retention of information in working memory, which may be mediated by activity looping between the EC and the hippocampus. The researchers suggest that when incoming sensory information matches the information held in working memory, this propels synchronous activity in the circuit.—Michele Solis.
Yamamoto J, Suh J, Takeuchi D, Tonegawa S. Successful Execution of Working Memory Linked to Synchronized High-Frequency Gamma Oscillations. Cell . 2014 Apr 23. Abstract