No abstract

1The lateral entorhinal cortex (LEC) is a critical structure for episodic memory, but the 2 roles of discrete neuronal populations within LEC are unclear. Here, we establish an 3 approach for selectively targeting fan cells in layer 2 (L2) of LEC. Whereas complete 4 lesions of the LEC were previously found to abolish associative recognition memory, 5 we find that after selective suppression of synaptic output from fan cells mice still 6 recognise novel object-context configurations, but are impaired in recognition of 7 novel object-place-context associations. Our experiments suggest a segregation of 8 memory functions within LEC networks and indicate that specific inactivation of fan 9 cells leads to behavioural deficits reminiscent of early stages of Alzheimer's disease. 10

Lateral entorhinal cortex (LEC) has been hypothesized to process nonspatial, item information that is combined with spatial information from medial entorhinal cortex to form episodic memories within the hippocampus. Recent studies, however, have demonstrated that LEC has a role in integrating features of episodic memory prior to the hippocampus. While the precise role of LEC is still unclear, anatomical studies show that LEC is ideally placed to be a hub integrating multisensory information.The current study tests whether the role of LEC in integrating information extends to long-term multimodal item-context associations. In Experiment 1, male rats were trained on a context-dependent odor discrimination task, where two different contexts served as the cue to the correct odor. Rats were pretrained on the task and then received either bilateral excitotoxic LEC or sham lesions. Following surgery, rats were tested on the previously learned odor-context associations. Control rats showed good memory for the previously learned association but rats with LEC lesions showed significantly impaired performance relative to both their own presurgery performance and to control rats. Experiment 2 went on to test whether impairments in Experiment 1 were the result of LEC lesions impairing either odor or context memory retention alone. Male rats were trained on simple odor and context discrimination tasks that did not require integration of features to solve. Following surgery, both LEC and control rats showed good memory for previously learned odors and contexts. These data show that LEC is critical for long-term odor-context associative memory.