Impaired Spatial Representation in CA1 after Lesion of Direct Input from Entorhinal Cortex

Abstract

Place-specific firing in the hippocampus is determined by path integration-based spatial representations in the grid-cell network of the medial entorhinal cortex. Output from this network is conveyed directly to CA1 of the hippocampus by projections from principal neurons in layer III, but also indirectly by axons from layer II to the dentate gyrus and CA3. The direct pathway is sufficient for spatial firing in CA1, but it is not known whether similar firing can also be supported by the input from CA3. To test this possibility, we made selective lesions in layer III of medial entorhinal cortex by local infusion of the neurotoxin gamma-acetylenic GABA. Firing fields in CA1 became larger and more dispersed after cell loss in layer III, whereas CA3 cells, which receive layer II input, still had sharp firing fields. Thus, the direct projection is necessary for precise spatial firing in the CA1 place cell population.

Loss of dendritic inhibition in the hippocampus after repeated early-life hyperthermic seizures in rats

“…Reduction in apical dendritic inhibition in CA1 may result in a loss of behavioral function of the hippocampus. In particular, a loss of distal dendritic inhibition in seizure rats may affect spatial coding by a direct entorhinal to CA1 distal-dendritic excitation (Brun et al, 2008;Leung, 2011). Abnormal place cell activity was found in animals with early-life seizures (Dube et al, 2009(Dube et al, , 2010.…”

Interaction of nucleus reuniens and entorhinal cortex projections in hippocampal field CA1 of the rat

“…Cognitive alterations resulting from experimental manipulations of RE (i.e., lesions, reversible inactivation, optogenetic stimulation) support the idea that, instead of specifically affecting the functioning of either the mPFC or hippocampus, RE is mainly involved in orchestrating the flow of hippocampal-mPFC information, likely by modulating the coupling between both structures (Viana di Prisco and Vertes 2006;Saalmann 2014;Cassel and 4 Pereira Ito et al 2015;Pereira de Vasconcelos and Cassel 2015). The EC has also been shown to play a role in various cognitive tasks (e.g., Skelton and McNamara 1992;Sybirska et al 2000;Remondes and Schumann 2004;Brun et al 2008;Deshmuk and Knierum 2011;Suh et al 2011;Wilson et al 2013;Chao et al 2015;Anderson et al 2015), and both RE and EC appear to be involved in the consolidation of hippocampal-dependent memories (Remondes and Schumann 2004;Loureiro et al 2012). Moreover, Xu and Sűdhof (2013) have proposed that the cooperativity between RE-CA1 and EC-CA1 input may reduce the threshold for synaptic plasticity, and thus for the incorporation of entorhinal-transmitted neocortical information in hippocampal memory representation and subsequent long-term storage.…”

Cosine Directional Tuning of Theta Cell Burst Frequencies: Evidence for Spatial Coding by Oscillatory Interference

“…However, hippocampal place cells can continue to exhibit spatial firing (and retain some theta modulation of their spike trains) after disruption of ascending theta pathways (Mizumori et al, 1989;Sharp and Koester, 2008;Koenig et al, 2011), after loss of inputs from entorhinal cortex (Van Cauter et al, 2008;Brun et al, 2008a), and before the development of entorhinal grid cells in rat pups (Wills et al, 2010). One explanation for this pattern of findings could be that place cells receive diverse VCO inputs from both direct (e.g., theta cells) and indirect (e.g., grid or boundary vector cells) sources, and any of these inputs may be sufficient to support some degree of spatial firing by place cells after other inputs are lost.…”