The MTL and the human entorhinal cortex synaptic currents in declarative memory – a study using fMRI and human microlaminar recordings

Aim: The human mesial temporal lobe (MTL) is involved in declarative memory. The exact contributions of MTL structures are still not understood. Using fMRI and human micro-electrode laminar recordings of the left entorhinal cortex (ER) we investigated the specific role of the MTL and the human ER in declarative memory and determined how neuronal excitation or inhibition are distributed across cortical layers in the ER during memory processes.

Methods: We used rapid event-related fMRI at 3T in 18 healthy, right handed subjects. The applied paradigm allowed the comparison of activity during episodic memory encoding versus retrieval, of episodic versus semantic memory, of memory for locations versus people, and of responses to novel versus repeated memory probes. The same task was applied to one 37-y old rh patient suffering from temporal lobe epilepsy (TLE) during fMRI. The patient was implanted with bilateral depth electrodes and one microlaminar electrode into the left ER. The use of micro-electrodes in humans offers unique insights into the laminar organization of memory processes in the ER. This method estimates synaptic current density and population firing in different cortical layers with millisecond temporal accuracy and spatial accuracy of ~200 m.

Results: FMRI: In the major comparisons, the MTL was activated during encoding and recall. The MTL and the hippocampal and parahippocampal structures showed the greater activation to semantic recall than to episodic recall.

Laminar recordings: We found that the ER is highly specific for when memories are retrieved as compared to when they are formed. The ER was slightly more involved in episodic retrieval than in semantic retrieval. There was no difference in neuronal activity towards novel / repeated stimuli or items for person / location. During recall, superficial cell layers receiving information from the association cortices were more active as deeper layers. During encoding, deeper cell layers, receiving input from the hippocampus showed the greatest activation.

Conclusion: Our data demonstrate that the ER is specific for retrieval and supports its specific role as a mediator between hippocampus and association cortices.

Acknowledgements: Supported by the USPHS (NS18741), MIND Institute, Förderverein Neurologie, Philipps-Universität Marburg and the Prof. Dr. Adolf Schmidtmann-Stiftung.