Professor Huibert D. Mansvelder Integrative Neurophysiology – Center for Neurogenomics and Cognitive Research (CNCR) Amsterdam

Mansvelder Huibert D

  • Alumni

Synaptic and Cellular Mechanisms Underlying Acetylcholinergic Actions on Cognition

About Professor Huibert D. Mansvelder

In several research lines, I aim at uncovering causal relationships between events at molecular, synaptic and cellular levels and cognitive behaviour. In particular, I focussed on the role of glutamatergic synaptic plasticity and underlying mechanisms in brain disorders such as drug addiction and mental retardation.

Using combinations of 2-photon calcium imaging, synaptic recordings, single-cell PCR, lentivirus-mediated targeted expression of nicotinic receptors and attention behavioural tests we identified the which neuronal elements in the PFC express nicotinic receptors and how they are altered by exposure to nicotine (Poorthuis, JNeurosci 2013; Poorthuis, Cerebral Cortex, 2013). In addition, we found mechanisms by which nicotine
alters the rules for synaptic plasticity (Couey, Neuron, 2007; Guillem, Science 2011). Recently, we uncovered mechanisms underlying long-term consequences of nicotine exposure during adolescence (Counotte, Nature Neuroscience, 2011; Goriounova JNeurosci 2012).

We found that re-exposure to environmental cues that have become associated with the use of drugs of abuse alter the molecular composition and function of glutamatergic synapses in the prefrontal cortex. Interfering with glutamatergic receptor endocytosis during cue exposure prevents relapse to drug taking (Van den Oever, Nature Neuroscience, 2008; Van den Oever, Neuropsychopharm, 2010)

By recording simultaneously up to six connected neurons in the prefrontal cortex of mouse models for mental retardation and autism, we found that at the short range, pyramidal neurons in the PFC have a higher probability of being connected (Testa-Silva, Cerebral Cortex, 2012). We observed that cortical synaptic plasticity of glutamatergic synapses in mental retardation is impaired due to unreliable dendritic calcium signalling.
Environmental enrichment restores these deficits (Meredith, Neuron, 2007), suggesting that increased neuronal activation alters cortical development in mental retardation.

We have found that networks of cortical pyramidal neurons and interneurons synchronize their activity to different rhythms arising from different cortical layers in response to cholinergic receptor activation. Information on timing is encoded both in excitatory and inhibitory synaptic inputs (Van Aerde, Journal of Physiology, 2009; Min, Journal of Neuroscience, 2010; Roa-Ruiz, Nature Neuroscience 2011; Heistek, JPhysiol 2013).

Ultimately, we would like to understand how neuronal networks of synaptically connected neurons in the human brain function. To this end, we collaborate at the Neuroscience Campus Amsterdam with neurosurgeon dr. JC Baayen. By recording from acute brain slices of human brain tissue that had to be removed from patients for the treatment of deeper structures (Tumors, epilepsy), we study mechanisms underlying the rules for associative plasticity at adult human neocortical synapses (Testa-Silva, Front Syn Neurosci 2010; Verhoog, JNeurosci 2013). We find that in line with psychophysical findings in human subjects that human synapses can associate synaptic events in a much wider time window than rodent synapses, and that L-type voltage-gated calcium channels underlie these properties.

Please see also:

5 Selected Publications

Yan P., Acker CD., Zhou WL., Lee P., Bollensdorff C., Negrean A., Lotti J., Sacconi L., Antic SD., Kohl P., Mansvelder HD., Pavone FS., Loew LM. (2012) Palette of fluorinated voltagesensitive hemicyanine dyes. Proc Natl Acad Sci U S A., 109 (50): 20443-8.

Guillem K., Bloem B., Poorthuis RB., Loos M., Smit AB., Maskos U., Spijker S., Mansvelder HD. (2011). Nicotinic acetylcholine receptor β2-subunits in the medial prefrontal cortex control attention. Science, 333 (6044): 888-91.

Rao-Ruiz P., Rotaru DC., Van der Loo RJ., Mansvelder HD., Stiedl O., Smit AB., Spijker S. (2011) Dorsohippocampal retrieval-specific endocytosis of GluA2 containing AMPARs is critical for reconsolidation of emotional memories. Nat. Neurosci., 14 (10): 1302-8.

Ridder MC., Boor I., Lodder JC., Postma NL., Duarri A., Van Minnen J., Brussaard AB., Estevez R., Scheper G., Mansvelder HD., Van der Knaap M. (2011) Megalencephalic leukoencephalopathy with cysts: oedema due to a defect in brain volume regulation. Brain., 134 (Pt11): 3342-54.

Witte S., Negrean A., Lodder JC., de Kock CPJ., Testa Silva G., Mansvelder HD., Groot ML. (2011) Label-free live brain imaging and targeted patching with third-harmonic generation microscopy. Proc Natl Acad Sci U S A., 108 (15): 5970-5.

Awards, Fellowships and Honours

2011            European Research Council (ERC) Starting grant (consolidator)
2006            Selected to the Young Academy of the Royal Society
2006            NWO VIDI award
2002            NWO ZonMW fellowship
2002            KNAW scholarship
1999            NWO Talent stipend
1994            Unilever Research Prize for outstanding undergraduate research
1994            Graduated ‘cum laude’

Technical Expertise

  • Neurophysiological techniques: imaging and electrophysiology
  • Multi-patch recordings
  • Brain slice recordings
  • Two-photon imaging
  • Multi-electrode array (MEA) recordings and analysis