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Swammerdam Institute for Life Sciences (SILS)

SILS research lines within ABC

The Institute

The Swammerdam Institute for Life Sciences (SILS) is a multidisciplinary research institute within the Faculty of Science (FNWI) with the aim to understand the functioning of a living cell. Within SILS, the Center for NeuroScience (SILS-CNS) consists of the groups working in the field of neuroscience. The mission of SILS-CNS is to understand plasticity in the brain, in relation to epilepsy, stress and depression, as well as cognition and emotion. The brain is studied in an integrated manner, from the level of the molecule, cell, network, all the way up to the organism.

sils.uva.nl

Memory consolidation and off-line reactivation of neural activity

Programme coordinator: Prof. dr. Cyriel Pennartz

Subject: Our subject of study is the intricate neural machinery that mediates the storage of information in long-term memory. Both procedural and declarative forms of memory are considered. In particular, we observe neural activity in brain structures that become active "off-line", i.e. after performance of a task has been completed and the subject is resting or sleeping, and that reactivate previously acquired information. We examine how such activity correlates and causally contributes to memory consolidation. This research line combines research in humans (using e.g. fMRI) and in freely moving rodents (using tetrodes and ensemble recordings).

Key publications:

  • Pennartz CMA, Lee E, Verheul J, Lipa P, Barnes CA, McNaughton BL. (2004). The ventral striatum in off-line processing: ensemble reactivation during sleep and modulation by hippocampal ripples. J. Neurosci., 24, 6446-6456.
  • Daselaar SM, Fleck MS, Prince SE, Cabeza R. (2006). The medial temporal lobe distinguishes old from new independently of consciousness. J Neurosci., 26, 5835-5839.
  • McNaughton BL, Battaglia FP, Jensen O, Moser EI, Moser MB. (2006). Path integration and the neural basis of the ‘cognitive map’. Nature Rev Neurosci., 7, 663-678.

Emotional memory, evaluation and attention

Programme coordinator: Prof. dr. Cyriel Pennartz

Subject: It is well known that brain structures such as the amygdala, orbitofrontal cortex and ventral striatum are involved in affective processing. These areas generate neural representations of expectation about future rewards or punishments, based on environmental cues and contexts. Here we investigate, first, how ensembles of neurones in the orbitofrontal cortex generate and shape neural correlates of reward expectation during learning. Second, we manipulate this formation of neural representations by locally applying dopaminergic and glutamatergic compounds. Third, we study how stimulus-reward associations guide attention and attentional set shifting and affect its neural correlates in the medial prefrontal cortex. Finally, reward-related firing patterns are studied in relation to mass oscillations in the prefrontal region and are being pursued in transgenic mouse models.

Key publications:

  • Voorn P, Vanderschuren LJMJ, Groenewegen HJ, Robbins TW, Pennartz CMA. (2004). Putting a spin on the dorsal-ventral divide of the striatum. Trends Neurosci., 27, 468-474.
  • Mulder AB, Nordquist RE, Örgüt O, Pennartz CMA. (2003). Learning-related changes in response patterns of prefrontal neurons during instrumental conditioning. Behav. Brain Res., 146, 77-88.

Modulation and plasticity of pre- and postsynaptic signalling

Programme coordinator: Prof. dr. Cyriel Pennartz

Subject: In this research line we investigate the subcellular processes underlying the types of neural plasticity studied in the first two mentioned lines, using neurochemical methods and in vitro patch-clamp. An important component of affective processing in the ventral striatum, for instance, appears to be a lateral inhibition, taking effect between the principal striatal neurons at high density. We study the dynamics of these inhibitory processes in relation to the release of the amino-acid transmitter GABA and the slower release of modulatory peptides. Differential dependence of these neurotransmitter classes on intracellular calcium is being studied. Two-photon microscopy is enabling us to investigate synaptic plasticity and intracellular calcium dynamics in vivo.

Key publications:

  • Pennartz CMA, De Jeu MTG, Bos NPA, Schaap J, Geurtsen AMS. Diurnal modulation of pacemaker potentials and calcium current in the mammalian circadian clock. Nature 2002, 416, 286-290.
  • Taverna S, Van Dongen, Y, Groenewegen, HJ, Pennartz CMA. Direct physiological evidence for synaptic connectivity between medium-sized spiny neurons in rat nucleus accumbens in situ. J. Neurophysiol. 2004, 91, 1111-1121.
  • Ghijsen, WEJM, Leenders, AGM, Differential signaling in presynaptic neurotransmitter release. Cell. Mol. Life Sci. 2005, 62, 937-954.

Effects of stress on learning and plasticity

Programme coordinator: Prof. dr. Marian Joëls and Dr. Harm Krugers

Subject: We study the effect of stress hormones on molecular, cellular and network properties of limbic neurons, and the relevance of these effects for learning and memory. This is studied after acute stress, but also in relation to chronic unpredictable stress, long-lasting consequences of early life stress and the cognitive deficits in stress-related disorders such as major depression and post-traumatic stress disorder.

Key publications:

  • Joëls M, Baram TZ. (2009) The neuro-symphony of stress. Nature Rev Neurosci, in press.
  • Champagne DL, Bagot RC, van Hasselt F, Ramakers G, Meaney MJ, de Kloet ER, Joëls M, Krugers H. (2008). Maternal care and hippocampal plasticity: evidence for experience-dependent structural functioning, and differential responsiveness to glucocorticoids and stress. J Neurosci, 28, 6037-6045.
  • Joëls M, Pu Z, Wiegert O, Oitzl MS, Krugers HJ. (2006). Learning under stress: how does it work? Trends in Cognitive Sciences, 10,152-8.

Structural plasticity in relation to stress and disease

Programme coordinator: Dr. Paul Lucassen

Subject: Stem cells in the adult brain generate new neurons in animals and humans, a process called "adult neurogenesis". Our main interest is the functional role of neurogenesis and its relevance for brain function, depression and dementia. In addition to cortex and amygdala, we focus on the hippocampus since it is affected in both these diseases, very sensitive to stress and implicated in learning and memory. We examine structural and functional plasticity after (early life) stress, during dementia-related events, and address whether manipulation of neurogenesis can affect brain function.

Key publications:

  • Oomen CA, Girardi CE, Cahyadi R, Verbeek EC, Krugers H, Joëls M, Lucassen PJ. (2009). Opposite effects of early maternal deprivation on neurogenesis in male versus female rats. PLoS ONE, 4, e3675.
  • Boekhoorn K, Terwel D, Biemans B, Borghgraef P, Wiegert O, Ramakers GJ, de Vos K, Krugers H, Tomiyama T, More H, Joëls M, van Leuven F, Lucassen PJ. (2006). Improved long-term potentiation and memory in young tau-P301L transgenic mice before onset of hyperphosphorylation and tauopathy. J Neurosci., 26, 3514-23.
  • Vreugdenhil E, Kolk SM, Boekhoorn K, Fitzsimons C, Schaaf M, Schouten T, Sarabdjitsingh A, Sibug R, Lucassen PJ (2007). Doublecortin-like, a microtubule associated protein expressed in radial glia is crucial for neuronal precursor division and radial process stability. Eur J Neurosci, 25, 635-648.

Excitability scaling in cognitive neuronal networks

Programme coordinator: Prof. dr. Wytse Wadman

Subject: Plasticity and adaptation as occur in learning and some forms of disease could shift neurons outside their working range. We are investigating the functional and molecular properties of homeostatic control mechanisms that stabilise neuronal excitability. We study scaling mechanisms at the single cell and at the network level. The involvement of Ca2+ dynamics in the process, the role of oscillations and memory consolidation are evaluated. Furthermore we investigate scaling deregulation in the diseased brain, particularly in epileptogenesis. The neurophysiological experiments are supported by mathematical and computational modeling.

Key publications:

  • Van Welie I, van Hooft JA, Wadman WJ. (2004). Homeostatic scaling of neuronal excitability by synaptic modulation of somatic hyperpolarization-activated Ih channels. Proc Natl Acad Sci USA, 101, 5123-8.
  • Kager H, Wadman WJ, Somjen GG. (2002). Conditions for the triggering of spreading depression studied with computer simulations. Journal of Neurophysiology, 88(5):2700-2712.

Basic mechanisms and therapeutic applications of deep brain stimulation

Programme coordinator: Prof. dr. Wytse Wadman

Subject: Direct interference with brain function using permanent implanted stimulation electrodes is a new successful approach in among others Parkinson's disease, epilepsy and depression. In this project we study the basic mechanisms that are involved and use that knowledge to design new stimulation protocols and paradigms. The work involves in-vitro measurements, but also measurements in epilepsy patients (in Ghent) and is supported by the industry (Philips Medical Systems).

Key publications:

  • Van Welie I, Remme MW, van Hooft JA, Wadman WJ. (2006). Different levels of Ih determine distinct temporal integration in bursting and regular-spiking neurons in rat subiculum. J Physiol, Jun 29.
  • Gorter JA, vanVliet E, Aronica E, Breit T, Rauwerda H, Lopes da Silva FH, Wadman WJ. (2006). Potential new anti-epileptogenic targets indicated by microarray analysis in a rat model for temporal lobe epilepsy, J.Neuroscience