André Fisahn Group
Neuronal synchronisation and network dynamics in health and neurodegenerative diseases
Rhythmic electrical activity in neuronal networks (network oscillations) is important for many higher functions in the brain, such as learning, memory and cognition. Such activity can be classed into different frequency bands, which are implicated in distinct processes and behaviors. In addition, network oscillations are altered or disrupted by various disorders of the nervous system such as Alzheimer's disease, schizophrenia and epilepsy, which can result in cognitive or behavioral impairments.
The main goal of our research is to increase our understanding of the cellular and synaptic mechanisms underlying neuronal synchronization and electrical oscillations in neuronal networks and to relate such knowledge to the changes observed in these network oscillations during pathological states of the brain such as Alzheimer’s disease, schizophrenia and epilepsy. Such knowledge is essential to understand pathological network changes and will enable us to find ways to rescue altered network oscillations in pathological states and define new targets for therapeutic intervention.
Using in vitro electrophysiology, imaging and modeling our research focuses mainly on gamma- and theta-frequency oscillations in the neuronal networks of the hippocampus and the medial septum, both of which play an important role in higher brain functions and are affected in various brain disorders:
- Amyloid-β Toxicity in Septo-Hippocampal Network Function - Implications for Alzheimer's Disease
- Prevention of Amyloidogenic Peptide-Induced Network and Cognitive Deficits by Activation of Peptide Degradation Mechanisms
- Reduction of Amyloid-β Toxicity by a-Helix-Ligands – Consequences for Neuronal Network Function
- Aminergic Modulation of Network Oscillations in the Rodent Hippocampus
Selected scientific publications
Amyloid-β-induced action potential desynchronization and degradation of hippocampal gamma oscillations is prevented by interference with peptide conformation change and aggregation.
Kurudenkandy FR, Zilberter M, Biverstål H, Presto J, Honcharenko D, Strömberg R, et al
J Neurosci 2014 Aug;34(34):11416-25
Interconnection and synchronization of neuronal populations in the mouse medial septum/diagonal band of Broca.
Leão RN, Targino ZH, Colom LV, Fisahn A
J Neurophysiol 2015 Feb;113(3):971-80
5-Hydroxytryptamine1A receptor-activation hyperpolarizes pyramidal cells and suppresses hippocampal gamma oscillations via Kir3 channel activation.
Johnston A, McBain CJ, Fisahn A
J Physiol 2014 Oct;592(19):4187-99
Medial septal dysfunction by Aβ-induced KCNQ channel-block in glutamatergic neurons.
Leão RN, Colom LV, Borgius L, Kiehn O, Fisahn A
Neurobiol Aging 2012 Sep;33(9):2046-61
Neuregulin and dopamine modulation of hippocampal gamma oscillations is dependent on dopamine D4 receptors.
Andersson RH, Johnston A, Herman PA, Winzer-Serhan UH, Karavanova I, Vullhorst D, et al
Proc Natl Acad Sci U S A 2012 Aug;109(32):13118-23
TrkB signaling in parvalbumin-positive interneurons is critical for gamma-band network synchronization in hippocampus.
Zheng K, An JJ, Yang F, Xu W, Xu ZQ, Wu J, et al
Proc Natl Acad Sci U S A 2011 Oct;108(41):17201-6
Kv7/KCNQ channels control action potential phasing of pyramidal neurons during hippocampal gamma oscillations in vitro.
Leão RN, Tan HM, Fisahn A
J Neurosci 2009 Oct;29(42):13353-64
Alpha-helix targeting reduces amyloid-beta peptide toxicity.
Nerelius C, Sandegren A, Sargsyan H, Raunak R, Leijonmarck H, Chatterjee U, et al
Proc Natl Acad Sci U S A 2009 Jun;106(23):9191-6
Muscarinic induction of hippocampal gamma oscillations requires coupling of the M1 receptor to two mixed cation currents.
Fisahn A, Yamada M, Duttaroy A, Gan JW, Deng CX, McBain CJ, et al
Neuron 2002 Feb;33(4):615-24
Cholinergic induction of network oscillations at 40 Hz in the hippocampus in vitro.
Fisahn A, Pike FG, Buhl EH, Paulsen O
Nature 1998 Jul;394(6689):186-9