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B2 - Effects of NR1 gene knockouts on PFC network dynamics

Principal investigator(s):

Abt. Klinische Neurobiologie des Universitätsklinikums und des DKFZ
DKFZ / A230
Im Neuenheimer Feld 280
69120 Heidelberg

Tel.:
0049-6221-42-3100 / 42-3101
Fax:
0049-6221-42-3111
Internet:
www.dkfz.de/de/klinische-neurobiologie/index.php
Email:
h.monyer@dkfz-heidelberg.de

Institute of Pathophysiology
University Medical Center
Johannes Gutenberg-University of Mainz
Duesbergweg 6
55128 Mainz

Tel.:
0049-6131-39-25005
Fax:
0049-6131-39-25560
Internet:
http://www.unimedizin-mainz.de/pathophysiologie/ag-prof-von-engelhardt.html
Email:
engelhardt@uni-mainz.de

Projects within the BCCN:


The entorhinal-hippocampal formation is necessary for the formation of episodic memories (what happened, where and when) and spatial navigation. In the hippocampus and entorhinal cortex, neurons exhibit particular spatial firing patterns in vivo; moreover, the entorhinal cortex is a main input and output area of the hippocampus. Therefore, we can assume that in both brain regions sensory and spatial information can be processed into complex representations of the external world, which in turn are necessary for a successful spatial navigation and the formation of episodic memories. The main objectives of subproject B2 comprised the functional analysis of specific excitatory and inhibitory cell types in the entorhinal cortex and/or hippocampus. To achieve this, we correlated behavioral studies with in vivo tetrode recordings in freely moving mice (Allen et al., 2014; Gil et al., submitted; Toader et al., submitted), optogenetics and Ca2+ imaging in anesthetized mice (Leitner et al., 2016). Of special interest for us was the contribution of inhibitory neurons in spatial (Toader et al., submitted) and olfactory coding (Leitner et al., 2016). Inhibitory neurons do not exhibit selective spatial firing and are less selective to olfactory cues-induced firing. However, they are key modulators in synchronizing large numbers of neurons. The coordinated activity of many neurons is essential for the generation of spatial, visual or olfactory representations.
The in vivo data we obtained in the entorhinal-hippocampal network prompted us to readjust the main object of the subproject B2 (instead of analyzing the effects of NR1 knock-out in the prefrontal cortex).
Our experimental data allude to real connectivity patterns in the entorhinal cortex thereby constraining postulated theoretical models. Moreover, the data give insight how the hippocampus and entorhinal cortex process information required for spatial or sensory information processing. Therefore, our data provide the basis for new, more realistic theoretical work.

Participating groups:


Key publications:

Gil M, Ancau M, Neitz A, Allen K, De Marco RJ, Monyer H (2017) Impaired path integration in mice with disrupted grid cell firing Nat. Neurosci., submitted .
Toader O, Gil M, Neitz A, Allen K, Monyer H (2017) Intact spatial coding in the medial entorhinal cortex of mice with impaired hippocampal function J. Neurosci., submitted .
Leitner FC, Melzer S, Lütcke H, Pinna R, Seeburg PH, Helmchen F, Monyer H (2016) Spatially segregated feedforward and feedback neurons support differential odor processing in the lateral entorhinal cortex Nat. Neurosci. 19(7): 935-944 .
Allen K, Gil M, Resnik E, Toader O, Seeburg P, Monyer H (2014) Impaired path integration and grid cell spatial periodicity in mice lacking GluA1-containing AMPA receptors J. Neurosci. 34: 6245-6259 .
Buetfering C, Allen K, Monyer H (2014) Parvalbumin interneurons provide grid cell-driven recurrent inhibition in the medial entorhinal cortex Nat. Neurosci. 17: 710-718 .