Impairment of spontaneous alternation behavior in sequential test procedures following mammillary body lesions in mice: evidence for time-dependent interference-related memory deficits.

The experiments reported here examined the effects of either radio frequency or kainic acid lesions of the median mammillary nucleus (MM) on spatial spontaneous alternation (SA) in mice. Animals were tested in a T-maze with sessions of six to nine successive trials given at varying intertrial intervals (ITIs). In the first experiment, conducted with an ITI of 30 s, damaged animals exhibited normal rates of SA on the second trial of the session but were progressively impaired on subsequent trials compared with controls. This finding was interpreted as an increased vulnerability to proactive interference. The second experiment was designed to investigate the effect of the ITI, and the results indicated that the previously observed impairment was completely suppressed by reducing the ITI from 30 s to 5 s. In order to further test our interference hypothesis, a third experiment was designed to investigate whether providing the animals with an extrinsic cue on one trial (5th) would increase the rate of SA on the subsequent (6th) trial (release from interference). Unexpectedly, results from this experiment showed that performance dramatically improved as soon as the cue was provided (i.e., on the 5th trial). These results are discussed in relation to a possible role of the mammillary bodies in memory processes. Specifically, it is suggested that as for Korsakoff patients, MM damaged mice suffer from an impaired ability to make temporal order judgments. Thus changing the context serves to help the animal actively reconstruct the sequence of past events.