Network structure determines patterns of network reorganization during adult neurogenesis

New cells are generated throughout life and integrate into the hippocampus via the process of adult neurogenesis. Epileptogenic brain injury induces many structural changes in the hippocampus, including the death of interneurons and altered connectivity patterns. The pathological neurogenic niche is associated with aberrant neurogenesis, though the role of the network-level changes in development of epilepsy is not well understood. In this paper, we use computational simulations to investigate the effect of network environment on structural and functional outcomes of neurogenesis. We find that small-world networks with external stimulus are able to be augmented by activity-seeking neurons in a manner that enhances activity at the stimulated sites without altering the network as a whole. However, when inhibition is decreased or connectivity patterns are changed, new cells are both less responsive to stimulus and the new cells are more likely to drive the network into bursting dynamics. Our results suggest that network-level changes caused by epileptogenic injury can create an environment where neurogenic reorganization can induce or intensify epileptic dynamics and abnormal integration of new cells.Comment: 28 pages, 10 figure

Simultaneous multi-patch-clamp and extracellular-array recordings: Single neuron reflects network activity

The increasing number of recording electrodes enhances the capability of capturing the network's cooperative activity, however, using too many monitors might alter the properties of the measured neural network and induce noise. Using a technique that merges simultaneous multi-patch-clamp and multi-electrode array recordings of neural networks in-vitro, we show that the membrane potential of a single neuron is a reliable and super-sensitive probe for monitoring such cooperative activities and their detailed rhythms. Specifically, the membrane potential and the spiking activity of a single neuron are either highly correlated or highly anti-correlated with the time-dependent macroscopic activity of the entire network. This surprising observation also sheds light on the cooperative origin of neuronal burst in cultured networks. Our findings present an alternative flexible approach to the technique based on a massive tiling of networks by large-scale arrays of electrodes to monitor their activity.Comment: 36 pages, 9 figure

Neuroplastic Changes Following Brain Ischemia and their Contribution to Stroke Recovery: Novel Approaches in Neurorehabilitation

Ischemic damage to the brain triggers substantial reorganization of spared areas and pathways, which is associated with limited, spontaneous restoration of function. A better understanding of this plastic remodeling is crucial to develop more effective strategies for stroke rehabilitation. In this review article, we discuss advances in the comprehension of post-stroke network reorganization in patients and animal models. We first focus on rodent studies that have shed light on the mechanisms underlying neuronal remodeling in the perilesional area and contralesional hemisphere after motor cortex infarcts. Analysis of electrophysiological data has demonstrated brain-wide alterations in functional connectivity in both hemispheres, well beyond the infarcted area. We then illustrate the potential use of non-invasive brain stimulation (NIBS) techniques to boost recovery. We finally discuss rehabilitative protocols based on robotic devices as a tool to promote endogenous plasticity and functional restoration

From network structure to network reorganization: implications for adult neurogenesis

Networks can be dynamical systems that undergo functional and structural reorganization. One example of such a process is adult hippocampal neurogenesis, in which new cells are continuously born and incorporate into the existing network of the dentate gyrus region of the hippocampus. Many of these introduced cells mature and become indistinguishable from established neurons, joining the existing network. Activity in the network environment is known to promote birth, survival and incorporation of new cells. However, after epileptogenic injury, changes to the connectivity structure around the neurogenic niche are known to correlate with aberrant neurogenesis. The possible role of network-level changes in the development of epilepsy is not well understood. In this paper, we use a computational model to investigate how the structural and functional outcomes of network reorganization, driven by addition of new cells during neurogenesis, depend on the original network structure. We find that there is a stable network topology that allows the network to incorporate new neurons in a manner that enhances activity of the persistently active region, but maintains global network properties. In networks having other connectivity structures, new cells can greatly alter the distribution of firing activity and destroy the initial activity patterns. We thus find that new cells are able to provide focused enhancement of network only for small-world networks with sufficient inhibition. Network-level deviations from this topology, such as those caused by epileptogenic injury, can set the network down a path that develops toward pathological dynamics and aberrant structural integration of new cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/85406/1/ph10_4_046008.pd

Information processing in a midbrain visual pathway

Visual information is processed in brain via the intricate interactions between neurons. We investigated a midbrain visual pathway: optic tectum and its isthmic nucleus) that is motion sensitive and is thought as part of attentional system. We determined the physiological properties of individual neurons as well as their synaptic connections with intracellular recordings. We reproduced the center-surround receptive field structure of tectal neurons in a dynamical recurrent feedback loop. We reveal in a computational model that the anti-topographic inhibitory feedback could mediate competitive stimulus selection in a complex visual scene. We also investigated the dynamics of the competitive selection in a rate model. The isthmotectal feedback loop gates the information transfer from tectum to thalamic rotundus. We discussed the role of a localized feedback projection in contributing to the gating mechanisms with both experimental and numerical approaches. We further discussed the dynamics of the isthmotectal system by considering the propagation delays between different components. We conclude that the isthmotectal system is involved in attention-like competitive stimulus selection and control the information coding in the motion sensitive SGC-I neurons by modulating the retino-tectal synaptic transmission