Neurobiology of Memory

Research

Research Interests

• Neuronal correlates of memory encoding and retrieval in the hippocampus
• Neurobiological basis of age-associated memory impairment
• Neurobiological basis of memory loss in Alzheimer’s disease

Subjects

• young and aged rats
• transgenic mice carrying human APP and PS1 mutations as a model of Alzheimer’s disease
• APP/PS1 mice cross-bred with mouse lines with altered growth factors or immunomodulators

Methods

• Local and systemic drug administration, dietary manipulations
• Behavioral testing batteries for learning and memory and general behavior in rats and mice
• Electrophysiological recordings of cortical and hippocampal EEG, ERPs and LTP in freely moving rodents
• Electrophysiological recordings of hippocampal single units (place cells) in freely moving rodents
• In vitro field and path clamp recordings in hippocampal slices and cell lines
• In vivo microdialysis in freely moving rats and mice
• Determination of Aβ peptides with ELISA from brain and CSF samples
• Immunohistology for Aβ, reactive microglia and astrocytes, immediate early genes and phosphoproteins involved in memory consolidation

1. Hippocampal place field firing rate maps in a familiar and a new environment	2. Field responses to perforant path stimulationin the hippocampus in vivo	3. A mouse in the water maze in the search for the hidden platform
4. Progression of brain amyloid pathology in an APPswe/PS1dE9 mouse

Collaboration

Hippocampal Electrophysiology

• Asla Pitkänen, Dept. Neurobiology, A. I. Virtanen Institute, Univ. Kuopio, Finland
• Tibor Harkany, Inst. Medical Sciences, Univ. Aberdeen, Scotland, UK / Karolinska Institutet, Stockholm, Sweden
• Yuri Zilberter, Inserm U29 - INMED, Marseilles, France / Karolinska Institutet, Stockholm, Sweden
• Michael Rowan, Trinity College, Dublin, Ireland
• Melitta Schachner, ZMBH, Hamburg, Germany
• J Matias Palva, Dept. Biosciences, Univ. Helsinki, Finland
• Esa Mervaala, Dept. Clinical Neurophysiology, Kuopio University Hospital, Finland

Mechanisms of Memory Loss in Alzheimer's Disease

• Jari Koistinaho, Dept. Neurobiology, A.I.Virtanen Institute, Univ. Kuopio, Finland
• Michael Courtney, Dept. Neurobiology, A.I.Virtanen Institute, Univ. Kuopio, Finland
• Hilkka Soininen, Dept. Neurology, Kuopio University Hospital, Finland
• Mikko Hiltunen, Dept. Neurology, Univ. Kuopio, Finland
• Riitta Miettinen, Dept. Neurology, Univ. Kuopio, Finland
• Markku Laakso, Dept. Internal Medicine, Kuopio University Hospital, Finland
• Reijo Karjalainen, Dept. Applied Biotechnology, Univ. Kuopio, Finland
• Heikki Rauvala, Neuroscience Center, Univ. Helsinki, Finland
• Eero Castren, Neuroscience Center, Univ. Helsinki, Finland
• Sabrina Davis, CNRS, Universite Paris Sud, Orsay, France
• Tobias Hartmann, ZMBH, Heidelberg, Germany
• Amanda Kiliaan, Dept. Anatomy, Univ. Nigmegen, Netherlands
• Vladimir Dolezaal, Chech Academy of Science, Prague, Chech Republic
• Botond Penke, Dept. Medical Chemistry, Univ. Szeged, Hungary
• Dieter Lütjohann, Dept. Clinical Pharmacology, Univ. Bonn, Germany
• David Borchelt, Univ. South Florida, Gainsville, FL, USA
• Pradeep Banerjee, Forest Research Laboratories, NJ, USA

Coordination of EU-wide projects

• Mechanisms of Memory loss in Alzheimer's disease, MEMOLOAD, EU 7th framework Program, Health
  http://www.uku.fi/MEMOLOAD/

Selected Publications

• Cho YH, Giese KP, Tanila H, Silva A, Eichenbaum H. Abnormal hippocampal spatial representations in alphaCaMKIIT286A and CREBalphaDelta-mice.  Science 279:867-869, 1998.

• Tanila H. Hippocampal place cells can develop distinct representations of two visually identical environments. Hippocampus 9(3):235-246, 1999.

• Eichenbaum H, Dudchenko P, Wood E, Shapiro M, Tanila, H. The hippocampus, memory, and place cells: Is it spatial memory or a memory space? Neuron 23:209-226; 1999.

• Puoliväli J, Wang J, Heikkinen T, Heikkilä M, Tapiola T, van Groen T, Tanila H. Hippocampal A beta 42 levels correlate with spatial memory deficit in APP and PS1 double transgenic mice. Neurobiol Dis 9(3):339-347, 2002.

• Ikonen S, McMahan R, Gallagher M, Eichenbaum H, Tanila H. Cholinergic system regulation of spatial representation by the hippocampus. Hippocampus 12:386-397, 2002.

• Gureviciene I, Ikonen S, Gurevicius K, Sarkaki A, van Groen T, Pussinen R, Ylinen A, Tanila H. Normal Induction but Accelerated Decay of LTP in APP + PS1 Transgenic Mice. Neurobiol Disease 15: 188-195, 2004.

• Pihlajamäki M, Tanila H, Könönen M, Hänninen T, Hämäläinen A, Soininen H, Aronen H. Visual presentation of novel objects and new spatial arrangements of objects differentially activates the medial temporal lobe subareas in humans.  Eur J Neurosci 19:1939-1949, 2004.

• Wilson IA, Ikonen S, Gureviciene I, McMahan RW, Gallagher M, Eichenbaum H, Tanila H. Cognitive Aging and the Hippocampus: How Old Rats Represent New Environments. J Neurosci 24:3870-3878, 2004.

• Minkeviciene R, Banerjee P, Tanila H. Memantine improves spatial learning in a transgenic mouse model of Alzheimer’s disease. JPET 311:677-682, 2004.

• Yavich L, Tanila H, Vepsäläinen S, Jäkälä P. Role of alpha-synuclein in presynaptic dopamine recruitment. J Neurosci 24:11165-11170, 2004.

• Wilson IA, Ikonen S, Gallagher M, Eichenbaum H, Tanila H. Age-associated alterations of hippocampal place cells are subregion specific. J Neurosci 25:6877-6886, 2005.

• Oksman M, Iivonen H, Hogyes E, Amtul Z, Penke B, Leenders I, Broersen L, Lütjohann D, Hartmann T, Tanila H. Impact of different saturated fatty acid, polyunsaturated fatty acid and cholesterol containing diets on beta-amyloid accumulation in APP/PS1 transgenic mice. Neurobiol Dis 23:563-572, 2006.

• Wilson I, Gallagher M, Eichenbaum H, Tanila H. Neurocognitive Aging: prior memories hinder new hippocampal encoding. Trends Neurosci. 29:662-670, 2006.

• Malm TM, Iivonen H, Goldsteins G, Keksa-Goldsteine V, Ahtoniemi T, Kanninen K, Salminen A, Auriola S, Van Groen T, Tanila H, Koistinaho J. Pyrrolidine dithiocarbamate activates Akt and improves spatial learning in APP/PS1 mice without affecting beta-amyloid burden. J Neurosci. 27:3712-3721, 2007.

• Hooijmans CR, Rutters F, Dederen PJ, Gambarota G, Veltien A, van Groen T, Broersen LM, Lutjohann D, Heerschap A, Tanila H., Kiliaan A. Changes in cerebral blood volume and amyloid pathology in aged Alzheimer APP/PS1 mice on a docosahexaenoic acid (DHA) diet or cholesterol enriched typical western diet. Neurobiol Dis 28:16-29, 2007.

• Machovį E, Jakubķk J, Michal P, Oksman M, Iivonen H, Tanila H, Dole˛al V. Impairment of muscarinic transmission in transgenic APPswe/PS1dE9 mice. Neurobiol Aging 29:368-378, 2008.

• Minkeviciene R, Ihalainen J, Malm T, Matilainen O, Keksa-Goldsteine V, Goldsteins G, Iivonen H, Leguit N, Glennon J, Koistinaho J, Banerjee P, Tanila H. Age-related decrease in stimulated glutamate release and vesicular glutamate transporters in APP/PS1 transgenic and wild-type mice. J Neurochem 105:584-594, 2008.

• Minkeviciene R, Rheims S, Dobszay MB, Zilberter M, Hartikainen J, Fülöp L, Penke B, Zilberter Y, Harkany T, Pitkänen A, Tanila H. Amyloid β-induced neuronal hyperexcitability triggers progressive epilepsy. J Neurosci 2009 (in press).