FNWI building SILS-CNS part 1
FNWI building SILS-CNS part 2

SILS Swammerdam Institute for Life Sciences - CNS





Research project Hemi Malkki :

Lost in consolidation - How deficiencies in memory consolidation affect
neural representations of spaces and events




Amsterdam Science Park


The role of hippocampus in various cognitive processes such as formation of long-term memories and spatial navigation has been puzzling scientists since the famous reports on patient H.M. After the infamous surgery to cure his epilepsy, H.M.’s medial temporal lobe, including hippocampus, was left severely dysfunctional, impairing his ability to form novel long-term memories as well as interfering with his spatial perception while his procedural skills were intact.



This in situ -hybridization in the hippocampus illustrates the rapid transportation of Arg3.1 mRNA to the dendrites upon activation




Arc protein expression in the hippocampus
Pictures by Claudia Mahlke (University of Hamburg)



Arc/Arg3.1 is a gene that codes an activity-regulated cytoskeletal protein which is involved in AMPA-receptor trafficking and is expressed e.g. during spatial exploration. Electrophysiological studies have shown it to be crucial for long-term synaptic plasticity (LTP and LTD). Moreover, behavioral studies have revealed it plays an important role in memory consolidation. Memory consolidation is the gradual strengthening of memories over time, rendering them more resistant to interference and discruption. Disrupted Arc/Arg3.1 function severely impairs long-term memory(1) while leaving working memory and other functions intact – a pattern of impairment that is reminiscent of H.M.'s case.

In this project, we record hippocampal neural ensembles during waking 4 and sleep periods to enhance our understanding of the general principles underlying memory consolidation and spatial representation as well the role of Arc/Arg3.1 in them.

Research interests

The role of Arc/Arg3.1 in formation and stability of place fields 2 in novel and familiar environments 3

Memory consolidation, cognitive flexibility and reversal learning 1



Methods

Recordings :
   Programmable spatial tasks for mice
   Hippocampal recordings during task performance and sleep using ultralight-weight devices for tetrode arrays
   Neuralynx recording system & Ethovision monitoring system

Analysis :
   Spike sorting
   Programming in MatLab


Members

  • Hemi Malkki (PhD student)
  • Cyriel Pennartz (Professor)
  • Francesco Battaglia (Assistant Professor)
  • Laura Donga (Technician)
  •   

Collaborators

This project represents a collaboration with the group of Prof. Dr. Dietmar Kuhl and Dr. Claudia Mahlke.
Group of Molecular and Cellular Cognition, Center for Molecular Neurobiology, University of Hamburg



References

  • Hemi A.I. Malkki, Laura A.B. Donga, Sabine E. de Groot and NeuroBSIK Mouse Phenomics Consortium, Francesco P. Battaglia, Cyriel M.A. Pennartz (2011)
    Towards mouse models of perseveration: A heritable component in extinction of operant behavior in fourteen standard and recombinant inbred mouse lines
    Neurobiology of Learning and Memory Volume 96, Issue 2, September 2011, Pages 280-287    PDF

  • Malkki HAI, Donga AB, de Groot SE, Battaglia FP, NeuroBSIK
    Mouse Phenomics consortium and Pennartz CMA (2010)
    Heritability and dissociation of traits relevant for operant conditioning in mice
    Front. in Behav. Neurosci. Vol. 4, art. 171. doi: 10.3389/fnbeh.2010.00171.     abstract/PDF

  • Plath N et al. (2006)
    Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories
    Neuron 52: 437-44

  • Wilson MA, McNaughton BL. (1993) Dynamics of the hippocampal ensemble code for space
    Science 261: 993-995

  • Knierim JJ. (2002) Dynamic interactions between local surface cues, distal landmarks, and intrinsic circuitry in hippocampal place cells J. Neurosci. 22: 6254-6264

  • Battaglia FP, Kalenscher T, Cabral H, Winkel J, Bos J, Manuputy R,
    van Lieshout T, Pinkse F, Beukers H and Pennartz CMA (2009)
    The Lantern: an ultra-light microdrive for multi-tetrode recording
    in freely moving mice and other small animals     J. Neurosci. Meth. 178: 291-300




This page was last updated on 28 september 2011

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