BDNF and NT-3 Increase Velocity of Activity Front Propagation in Unidimensional Hippocampal Cultures

Abstract

Jacobi S, Soriano J, Moses E. BDNF and NT-3 increase velocity of activity front propagation in unidimensional hippocampal cultures. J Neurophysiol 104: 2932-2939, 2010. First published July 28, 2010 doi:10.1152/jn.00002.2010. Neurotrophins are known to promote synapse development as well as to regulate the efficacy of mature synapses. We have previously reported that in two-dimensional rat hippocampal cultures, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 significantly increase the number of excitatory input connections. Here we measure the effect of these neurotrophic agents on propagating fronts that arise spontaneously in quasi-one-dimensional rat hippocampal cultures. We observe that chronic treatment with BDNF increased the velocity of the propagation front by about 30%. This change is attributed to an increase in the excitatory input connectivity. We analyze the experiment using the FeinermanGolomb/Ermentrout-Jacobi/Moses-Osan model for the propagation of fronts in a one-dimensional neuronal network with synaptic delay and introduce the synaptic connection probability between adjacent neurons as a new parameter of the model. We conclude that BDNF increases the number of excitatory connections by favoring the probability to form connections between neurons, but without significantly modifying the range of the connections (connectivity footprint). I N T R O D U C T I O NNeurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) play important roles in neural development and survival. In particular, they were shown to play a critical role in controlling axonal and dendritic growth as well as maintenance of synaptic efficacy (Baker et al. 1998; Bartrup et al. 1997; Bolton et al. 2000; Labele and Leclerc 2000;Morfini et al. 1994;Vicario-Abejon et al. 1998). However, the majority of previously reported effects of the neurotrophins focused on the local changes that they induce in neuron morphology or synaptic connection strength. We have recently shown that in two-dimensional (2D) rat hippocampal cultures, neurotrophins also induce global changes in neural network connectivity (Jacobi et al. 2009). In particular, exposure to BDNF increased excitatory input connectivity, but without modifying the inhibitory connectivity, and that resulted in spontaneous activity bursts whose amplitude was insensitive to the blocking of inhibition.To further assess the relation between neurotrophic effects and neural connectivity, we consider here quasi-one-dimensional (1D) neural cultures, where neural activity propagation is restricted to a single path. One-dimensional neural cultures have emerged in the last years as versatile culturing platforms to investigate the relation between neuronal connectivity, signal propagation, and information coding (Feinerman et al. 2005;Golomb and Ermentrout 1999;Jacobi and Moses 2007;Osan and Ermentrout 2002). The key feature of 1D cultures is that the velocity of activity fronts depends on neural connectivity and specifically on both the synaptic ...

Rich dynamics and functional organization on topographically designed neuronal networks in vitro

“…The contrasting velocities of activity propagation in the tracks configuration, with measured velocities about 5 times larger along tracks than across them, can be put in context of theoretical models 51 , 52 and experiments on activity propagation in one-dimensional neuronal cultures. 53 , 54 , 55 These studies revealed that the velocity of activity fronts depended on average neuronal connectivity and synaptic strength. If we assume that synaptic strength is similar in all neurons in the culture, then we conclude that connectivity along tracks was 5-fold higher than transverse to it.…”

Rich dynamics and functional organization on topographically designed neuronal networksin vitro

“…The contrasting velocities of activity propagation in the tracks configuration, with measured velocities about 5 times larger along tracks than across them, can be put in context of theoretical models (Bressloff, 2000; Golomb and Ermentrout, 1999) and experiments on activity propagation in one-dimensional neuronal cultures (Feinerman et al, 2005; Jacobi et al, 2010; Jacobi and Moses, 2007). These studies revealed that the velocity of activity fronts depended on average neuronal connectivity and synaptic strength.…”

Neuronal Cultures: Exploring Biophysics, Complex Systems, and Medicine in a Dish

“…An idea that was particularly enlightening was the study of the velocity of propagating fronts. Some years ago, we showed experimentally and theoretically that the velocity of activity propagation depends on the average connectivity of the neurons and the balance between excitation and inhibition [62]. Thus, such a velocity analysis provides an elegant way to obtain indirect information on the connectivity of the network and its changes upon development or pharmacological action.…”