Structural and functional diversity of the axon initial segment of principal neurons in hippocampal ensembles

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We want to investigate whether the axon origin location can modulate input-output relations of neurons and if this makes a difference in the integration of cells into functional ensembles.

Action potentials (APs) are usually initiated in the axon initial segment (AIS), a highly specialized neuronal compartment. Recent evidence suggests that location and length of the AIS is a variable and independent determinant of neuronal excitability. Recently, we have found that the AIS branches off from basal dendrites rather than from the soma in about 50% of CA1 pyramidal cells. Our preliminary data show that such axon-carrying dendrites (AcD) are privileged sites for synaptic excitation, supporting facilitated action potential generation.

This conclusion is further corroborated by multi-compartment computer modelling incorporating AcDs as a structural feature. Therefore, diversity of AIS location in CA1 pyramidal cells may cause different input-dependent activation of neurons, thereby contributing to the definition of co-active ensembles. To test this hypothesis, we will first examine whether AP generation during CA1 network activity differs between pyramidal cells with somatic versus dendritic origin of the axon. Specifically, we will probe the differential role of perisomatic inhibition for AP generation in both types of neurons. Secondly, we will test whether neurons with similar morphology (i.e. those with somatic or dendritic origin of the axon, respectively) are differentially involved in the formation of spatio-temporal activity patterns: Are neurons of a given morphology more or less active than others? Are similar neurons more frequently co-active than different morphological types? Is one type of pyramidal cells a preferred member of neuronal ensembles during specific hippocampal network oscillations? Lastly, we will ask whether there are structural differences between AIS with a somatic vs. a dendritic origin. Together, our study on structure and function of CA1 pyramidal cell axons shall reveal whether the localization and structure of the AIS is a morphological determinant of network integration.
Thome C, Kelly T, Yanez A, Schultz C, Engelhardt M, Cambridge SB, Both M, Draguhn A, Beck H, Egorov AV (2014) Axon-Carrying Dendrites Convey Privileged Synaptic Input in Hippocampal Neurons. Neuron. 2014 Sep 17;83(6):1418-30
Pfeiffer T, Draguhn A*, Reichinnek S, Both M (2014) Optimized temporally deconvolved Ca2+ imaging allows identification of spatiotemporal activity patterns of CA1 hippocampal ensembles. NeuroImage pii:S1053-8119(14)00177-3

Gutzmann A, Ergül E, Grossmann R, Schultz C, Wahle P, Engelhardt M (2014) A period of structural plasticity at the axon initial segment in developing visual cortex. Front Neuroanat 8:11.

Zylla MM, Zhang XM, Reichinnek S, Draguhn A*, Both M (2013) Cholinergic plasticity of oscillating neuronal assemblies in mouse hippocampal slices. PLoS One 8:e80718.

Reichinnek S, von Kameke A, Hagenston AM, Freitag E, Roth FC, Bading H*, Hasan MT, Draguhn A*, Both M (2012) Reliable optical detection of coherent neuronal activity in fast oscillating networks in vitro. NeuroImage 60:139-152.

Bähner F, Weiss EK, Birke G, Maier N, Schmitz D, Rudolph U, Frotscher M, Traub RD, Both M§, Draguhn A*§ (2011) Cellular correlate of assembly formation in oscillating hippocampal networks in vitro. Proc Natl Acad Sci U S A 108:E607-616. § equal contribution

Reichinnek S, Künsting T, Draguhn A*, Both M (2010) Field Potential Signature of Distinct Multicellular Activity Patterns in the Mouse Hippocampus. J Neurosci 30:15441-15449.

Winkels R, Jedlicka P, Weise FK, Schultz C, Deller T, Schwarzacher SW (2009) Reduced excitability in the dentate gyrus network of betaIV-spectrin mutant mice in vivo. Hippocampus 7:677- 686.

Jedlicka P, Schwarzacher SW, Winkels R, Kienzler F, Frotscher M, Bramham CR, Schultz C, Bas Orth C, Deller T (2009) Impairment of in vivo theta-burst long-term potentiation and network excitability in the dentate gyrus of synaptopodin-deficient mice lacking the spine apparatus and the cisternal organelle. Hippocampus 19:130-140.

Politi C, Del Turco D, Sie JM, Golinski PA, Tegeder I, Deller T, Schultz C. (2008) Accumulation of phosphorylated I kappaB alpha and activated IKK in nodes of Ranvier. Neuropathol Appl Neurobiol. 34:357-365.

Both M, Bähner F, von Bohlen und Halbach O, Draguhn A* (2008) Propagation of specific network patterns through the mouse hippocampus. Hippocampus 18:899-908.

Bas Orth C, Schultz C, Müller CM, Frotscher M, Deller T (2007) Loss of the cisternal organelle in the axon initial segment of cortical neurons in synaptopodin-deficient mice. J Comp Neurol 504:441-449.

*Principal investigators of other projects within the CRC