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«1, 2* 1, 2 1, 2 1, 2 Mihael Zohar, Philipp Schnepel, Ad Aertsen and Clemens Boucsein University of Freiburg, Neurobiology and Biophysics, Germany ...»

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1, 2* 1, 2 1, 2 1, 2

Mihael Zohar, Philipp Schnepel, Ad Aertsen and Clemens Boucsein

University of Freiburg, Neurobiology and Biophysics, Germany University of Freiburg, Bernstein Center Freiburg, Germany Pyramidal neurons in layer V of the neocortex constitute a major output population of the cortical network. Due to their good accessibility and their intricate morphology, showing a prominent apical dendrite spanning all cortical layers and terminating in an expanded tuft, these cells have been utilized to characterize general principles of cellular physiology of cortical pyramidal cells. In particular, it has been shown that the apical dendrite and the soma undergo functional decoupling during maturation, resulting in a strong attenuation of EPSP’s arising from synapses located on the distal apical dendrite on their way to the soma. Furthermore, it was shown that apical dendrites of large layer V neurons are capable of active potential generation, such as Calcium- and NMDA-spikes.

While connectivity of the somata was, up to now, extensively examined with anatomical, paired recording and photo stimulation methods, little is known about which populations of neurons project to the distal dendrite and are, thus, mainly involved in the generation of active potentials in the distal dendrite.

Here we used an experimental approach employing simultaneous distal dendritic and somatic patch-clamp recordings in vitro together with presynaptic glutamate uncaging to examine the properties and layer-dependent projection patterns onto the two compartments of layer V pyramidal neurons within the rat somatosensory cortex.

With this new combination of methods we were able to detect inputs from presynaptic neurons with a lateral distance of more than 1mm in acute brain slices and to compare the functional input maps from soma and apical dendrite. As reported previously, a substantial fraction of connections gave rise to EPSP’s which underwent a strong attenuation along the apical dendrite and were hardly detectable at the soma. Surprisingly, however, the functional maps derived from dendritic vs. somatic recordings showed considerable differences in the layer in which the somata of the presynaptic neurons were located. While we could confirm the established projection patterns onto the soma, originating from cells in layers II/III, V and VI, the presynaptic neurons projecting onto the distal dendrite predominantly originate from supragranular layers. These compartment-specific projection patterns onto layer V pyramidal neurons point to a distributed integration of inputs coming from different cortical layers. These findings may help to further understand the role of dendritic integration in large layer V pyramidal cells, in particular the nonlinear mechanisms in the distal dendrite and the presynaptic populations involved in their generation.

Acknowledgements This project received funding from the German Federal Ministry of Education and Research (Grants 01GQ0420 to BCCN Freiburg and 01GQ0830 to BFNT Freiburg-Tübingen) and from the German Research Council (DFG-SFB 780).

Keywords: compartment, connectivity, dendrite, neurons, networks and dynamical systems, photo stimulation Conference: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011, Freiburg, Germany, 4 Oct - 6 Oct, 2011.

Presentation Type: Poster Topic: neurons, networks and dynamical systems (please use "neurons, networks and dynamical systems" as keywords) Citation: Zohar M, Schnepel P, Aertsen A and Boucsein C (2011). Compartment-specific projection patterns onto pyramidal cells in rat neocortex. Front. Comput. Neurosci.

Conference Abstract: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011. doi: 10.3389/conf.fncom.2011.53.00127 Received: 23 Aug 2011; Published Online: 04 Oct 2011.

* Correspondence: Mr. Mihael Zohar, University of Freiburg, Neurobiology and Biophysics, Freiburg, Germany, mihael.zohar@biologie.uni-freiburg.de

–  –  –

We studied the impact of neuronal heterogeneity on the spiking activities in a population of leaky integrate-and-fire neurons. In the high input regime, the sum of synaptic inputs to a neuron can be approximated by a fluctuating input noise, characterized by its mean and variance (Brunel & Hakim, 1999; Kuhn et al., 2004). Based on data from in vitro recordings (Padmanabhan and Urban, 2010) and new insights from mathematical analyses, we conclude that common input into heterogeneous neurons is better realized by an identical noise with different values of mean and variance than by the usual practice of adding independent noises to individual neurons. We identified the distinct roles of the mean and the variance for the spiking activity of a population of heterogeneous neurons. We found that the output firing rate of a neuron is largely shaped by the mean level of the noise, whereas the distributed values of the variance give rise to different degrees of imprecise spiking. To conclude, when receiving common input, heterogeneous neurons may differ considerably in their output firing rates, and their spikes may be jittered by several milliseconds, a phenomenon some researchers have termed “decorrelation” (Padmanabhan and Urban, 2010).





Acknowledgements Supported by the German Federal Ministry of Education and Research (BMBF 01GQ0420 “BCCN Freiburg” and BMBF 01GW0730 “Impulse Control”).

References Brunel, N., and Hakim, V. (1999). Fast global oscillations in networks of integrate-and-fire neurons with low firing rates. Neural Comp. 11(7), 1621–1671.

Kuhn, A., Aertsen, A., and Rotter, S. (2004). Neuronal integration of synaptic input in the fluctuation-driven regime. J. Neurosci. 24, 2345-2356.

Padmanabhan, K., and Urban, N. N. (2010). Intrinsic biophysical diversity decorrelates neuronal firing while increasing information content. Nat. Neurosci. 13(10), 1276–1282.

Keywords: imprecise spiking, neuronal heterogeneity, white noise Conference: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011, Freiburg, Germany, 4 Oct - 6 Oct, 2011.

Presentation Type: Poster Topic: neurons, networks and dynamical systems (please use "neurons, networks and dynamical systems" as keywords) Citation: Yim M, Aertsen A and Rotter S (2011). Impact of intrinsic neuronal heterogeneity on firing rates and spike train correlations. Front. Comput. Neurosci. Conference Abstract: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011. doi: 10.3389/conf.fncom.2011.53.00213 Received: 17 Aug 2011; Published Online: 04 Oct 2011.

* Correspondence: Miss. Man Yi Yim, University of Freiburg, Bernstein Center Freiburg, Freiburg, 79104, Germany, yim@bcf.uni-freiburg.de

–  –  –

Electrical stimulation of nervous tissue is increasingly used in the treatment of CNS disorders, in neurotechnological devices or in examining the physiological properties of single cells and the function of networks of neurons. Interactions between ongoing and evoked neuronal activity render the stimulus’ response sensitive to the network state and the history of previous activity. Here, we were interested in the interactions that arise between spontaneous and evoked network activity and how they shape and modulate stimulus-response relations. Our goal was to obtain analytical models for a user-defined interaction with neuronal activity.

We recorded and electrically stimulated rat cortical cell cultures on microelectrode arrays. Spontaneous network activity consisted of recurring periods of globally synchronized firing, so-called network bursts. The duration of intervals that preceded network bursts best predicted the length of the following network burst. Variable responses to electrical stimulation depended on the timing of stimulation relative to preceding network bursts. Response lengths increased exponentially and saturated with longer duration of pre-stimulus inactivity with y(t) = A(1-e-αt). Response delays, in turn, decreased exponentially and saturated at a low level with y(t) = Be-βt + C. User-defined timing of stimulation relative to spontaneous activity significantly reduced trial-by-trial variability and thus facilitated further examinations on state-dependent stimulus-response relations.

Disinhibition by blockage of GABAA-receptors yielded ~183 % more spikes per network burst with ~88 % longer intervals and unchanged overall firing rates. The modulation of response delays by the duration of pre-stimulus inactivity persisted under disinhibition. The correlation between distance to stimulation site and response delay was enhanced and the speed of propagation clearly depended on stimulus-timing.

Facilitation of synaptic transmission by overexpressing DOC2B, a synaptic protein mainly involved in vesicle priming and docking, yielded ~39 % more spikes per network burst and ~72 % longer intervals. The rate parameter β that describes the relation between recovery from pre-stimulus, burst-induced depression and response delay decreased in young networks ( 20 DIV) whereas it increased in old networks (≥ 20 DIV) with DOC2B. This suggested slower and faster recovery, mediated by e.g. vesicle replenishment, depending on the network’s maturation state.

In summary, we identified explicit rules for the modulation of evoked responses by spontaneous activity in generic neuronal networks in vitro. Our data support a process of network depression due to depletion of readily releasable vesicles during network bursts followed by subsequent recovery.

Acknowledgements This work was supported by the German BMBF (FKZ 01GQ0420 & FKZ 01GQ0830) and the Boehringer Ingelheim Fonds.

Keywords: DOC2B, dynamical systems, electrical stimulation, microelectrode array, networks, neurons, pre-stimulus activity, response variability Conference: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011, Freiburg, Germany, 4 Oct - 6 Oct, 2011.

Presentation Type: Poster Topic: neurons, networks and dynamical systems (please use "neurons, networks and dynamical systems" as keywords) Citation: Weihberger O, Lavi A, Okujeni S, Ashery U and Egert U (2011). Quantitative models for stimulus-response relations in neuronal networks in vitro. Front. Comput.

Neurosci. Conference Abstract: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011. doi:

10.3389/conf.fncom.2011.53.00059 Received: 23 Aug 2011; Published Online: 04 Oct 2011.

* Correspondence: Mr. Oliver Weihberger, University of Freiburg, Bernstein Center Freiburg, Freiburg, Germany, weihberger@bcf.uni-freiburg.de

–  –  –

A major challenge in the analysis of neural activity data when considering spikes as the main information carrying unit is the detection of sets of neurons which act as functional groups. Such neuronal cell assemblies can be identified by clustering the spectrum of zero-lag cross-correlation between all pairs of neurons in a network or by dimensionality reduction of the similarity matrix of the spike trains.

Here we investigate how the identification of cell assemblies is dependent on the methodology chosen. We construct a self similar network of inhibitory adaptive exponential integrate-and-fire neurons that is stimulated with Poissonian excitatory input. For such a network one would expect that groups of neurons show a similar activity as the network as a whole. However, we observe that there is a difference between the evolution of network activity and sets of neurons clustered according to their correlation. When analyzing medium spiny neuron calcium imaging data, we again find that the results of the two methods are not in line.

Acknowledgements Partially funded by the German Federal Ministry of Education and Research (BMBF 01GQ0420 to BCCN Freiburg, BMBF GW0542 Cognition and BMBF 01GW0730 Impulse Control), EU Grant 269921 (BrainScaleS), Helmholtz Alliance on Systems Biology (Germany), Neurex, the the Junior Professor Program of Baden-Württemberg and the Erasmus Mundus Joint Doctoral programme EuroSPIN.

References

1. Miller BR, Walker AG, Shah AS, Barton SJ, Rebec GV: Disregulated information processing by medium spiny neurons in striatum of freely behaving mouse models of Huntington's disease. J Neurophysiol 2008, 100:2205-2216.

2. Carrillo-Reid L, Tecuapetla F, Tapia D, Hernández-Cruz A, Galarraga E, Drucker-Colin R, Bargas J: Encoding network states by striatal cell assemblies. J Neurophysiol 2008, 99:1435-1450.

3. Ponzi A, Wickens J: Sequentially switching cell assemblies in random inhibitory networks of spiking neurons in the striatum. J Neurosci 2010, 30(17):5894-5911.

4. Sasaki T, Matsuki N, Ikegaya Y: Metastability of active CA3 networks. J Neurosci 2007, 27(3):517-528.

5. Brette R, Gerstner W. Adaptive exponential integrate-and-fire model as an effective description of neuronal activity. J Neurophysiol. 2005, 94(5):3637-42.

Keywords: Assemblies, Clustering, Dimensionality reduction, Medium Spiny Neurons, Self similar networks Conference: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011, Freiburg, Germany, 4 Oct - 6 Oct, 2011.

Presentation Type: Poster Topic: data analysis and machine learning (please use "data analysis and machine learning" as keyword) Citation: Toledo-Suárez C, Yim M, Kumar A and Morrison A (2011). Neuron versus Time Clustering in the Identification of Cell Assemblies. Front. Comput. Neurosci.

Conference Abstract: BC11 : Computational Neuroscience & Neurotechnology Bernstein Conference & Neurex Annual Meeting 2011. doi: 10.3389/conf.fncom.2011.53.00073 Received: 23 Aug 2011; Published Online: 04 Oct 2011.

* Correspondence: Mr. Carlos Toledo-Suárez, University of Freiburg, Freiburg, 79104, Germany, carlos.toledo@bcf.uni-freiburg.de

–  –  –



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