Neural circuits with long-distance axon tracts for determining functional connectivity

Tang-Schomer, Min D.; Davies, Paul; Graziano, Daniel; Thurber, Amy E.; Kaplan, David L.

doi:10.1016/j.jneumeth.2013.10.014

Cited by 15 publications

(10 citation statements)

References 51 publications

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“…Although microtunnel-like devices have an extensive history (Campenot, 1977 ), it is only recently that this technology has become popular in neuroscience research within dissociated (Taylor et al, 2003 , 2005 , 2009 ; Pearce et al, 2005 ; Berdondini et al, 2006 ; Morin et al, 2006 ; Ravula et al, 2007 ; Feinerman et al, 2008 ; Liu et al, 2008a ; Dworak and Wheeler, 2009 ; Park et al, 2009 ; Yang et al, 2009 ; Berdichevsky et al, 2010 ; Shi et al, 2010 ; Taylor and Jeon, 2010 ; Wieringa et al, 2010 ; Kanagasabapathi et al, 2011 , 2012 , 2013 ; Pan et al, 2011 ; Peyrin et al, 2011 ; Biffi et al, 2012 ; Bisio et al, 2014 ; Sung et al, 2014 ; Tang-Schomer et al, 2014 ) and organotypic culture (Berdichevsky et al, 2010 , 2012 ). In vitro neuronal cell-culture preparations used in combination with this technology may provide a promising new way to directly manipulate and study the effects of connection strength upon network activity under ideal conditions due to their accessibility and flexibility (Maeda et al, 1995 ; Potter, 2001 ; Pan et al, 2009b ; Levy et al, 2012 ).…”

Section: Introductionmentioning

confidence: 99%

An in vitro method to manipulate the direction and functional strength between neural populations

Pan

Alagapan

Franca

et al. 2015

Front. Neural Circuits

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We report the design and application of a Micro Electro Mechanical Systems (MEMs) device that permits investigators to create arbitrary network topologies. With this device investigators can manipulate the degree of functional connectivity among distinct neural populations by systematically altering their geometric connectivity in vitro. Each polydimethylsilxane (PDMS) device was cast from molds and consisted of two wells each containing a small neural population of dissociated rat cortical neurons. Wells were separated by a series of parallel micrometer scale tunnels that permitted passage of axonal processes but not somata; with the device placed over an 8 × 8 microelectrode array, action potentials from somata in wells and axons in microtunnels can be recorded and stimulated. In our earlier report we showed that a one week delay in plating of neurons from one well to the other led to a filling and blocking of the microtunnels by axons from the older well resulting in strong directionality (older to younger) of both axon action potentials in tunnels and longer duration and more slowly propagating bursts of action potentials between wells. Here we show that changing the number of tunnels, and hence the number of axons, connecting the two wells leads to changes in connectivity and propagation of bursting activity. More specifically, the greater the number of tunnels the stronger the connectivity, the greater the probability of bursting propagating between wells, and shorter peak-to-peak delays between bursts and time to first spike measured in the opposing well. We estimate that a minimum of 100 axons are needed to reliably initiate a burst in the opposing well. This device provides a tool for researchers interested in understanding network dynamics who will profit from having the ability to design both the degree and directionality connectivity among multiple small neural populations.

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Section: Introductionmentioning

confidence: 99%

An in vitro method to manipulate the direction and functional strength between neural populations

Pan

Alagapan

Franca

et al. 2015

Front. Neural Circuits

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“…In contrary, white matter is composed of long-range myelinated axon tracts and contains relatively very few cell bodies. In this context, we consider that one of the most reliable techniques to control the location of soma and neurite microcompartments within a defined neuronal network [41] is the micropatterning method ( Fig. 2A).…”

Section: Research Highlightmentioning

confidence: 99%

Dissecting the mechanical behavior of neuronal microcompartments by combining magnetic tweezers and protein micropatterns

Grevesse¹,

Lantoine²,

Delhaye³

et al. 2016

Neurosci Commun

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Alterations of the axonal morphology are key signatures of traumatic brain injury (TBI). Although the pathobiology of axonal injury has been extensively investigated, the vulnerability of the axonal microcompartment over the soma was still misunderstood. We hypothesized that the soma and the axon of neurons display opposite mechanical behaviors, rendering the axon more sensitive to a mechanical stress. To test this hypothesis, we used a microcontact printing method to control the growth of cortical neuron in a bipolar morphology and the viscoelastic properties of soma and axon microcompartments were measured with magnetic tweezers. Creep experiments showed that neuronal microcompartments exhibit distinct mechanical behaviors: the soma is softer and characterized by an elastic-like behavior, while the neurite is stiffer and viscous-like. By altering cytoskeletal filaments with pharmacological agents, we determined the origin of the compartmentalization of mechanical behaviors within cortical neurons. The nucleus determines the elastic and stress stiffening behavior of the soma, while the sliding of neurofilaments determines the viscous-like state of the neurite. In addition, our results revealed that at the contrary of the soma, the neurite can sense its mechanical environment and becomes softer and more viscous on soft surfaces, showing that, as for the mechanical behavior, the mechanosensitivity is localized to the neuronal microcompartments. Our findings shed light on the importance of the regionalization of neuronal properties to their microcompartments in response to a mechanical insult. Future works will need to investigate the relationship between the mechanical differences of neuronal microcompartments and their functions. In this context, we suggest to consider microprinted neuronal networks as an efficient tool for investigating the effect of the propagation of injury forces on the behavior of neuronal circuits.Keywords: Neuron; microcompartment; rheology; diffuse axonal injury; mechanosensitivity To cite this article: Thomas Grevesse, et al. Dissecting the mechanical behavior of neuronal microcompartments by combining magnetic tweezers and protein micropatterns. Neurosci Commun 2015; 1: e1003.

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“…Neural Plasticity AIS structure (Figure 1(e) and (f)). Although it is difficult to anticipate the consequences of these molecular changes since the cortical circuitry is fairly complex [59], these findings indicate that NaV1.6 functionality could be altered in BTBR mice. This led us to investigate other isoforms of NaV1 α subunits.…”

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confidence: 93%

Changes in the Fluorescence Tracking of NaV1.6 Protein Expression in a BTBR T+Itpr3tf/J Autistic Mouse Model

et al. 2019

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The axon initial segment (AIS), the site of action potential initiation in neurons, is a critical determinant of neuronal excitability. Growing evidence indicates that appropriate recruitment of the AIS macrocomplex is essential for synchronized firing. However, disruption of the AIS structure is linked to the etiology of multiple disorders, including autism spectrum disorder (ASD), a condition characterized by deficits in social communication, stereotyped behaviors, and very limited interests. To date, a complete understanding of the molecular components that underlie the AIS in ASD has remained elusive. In this research, we examined the AIS structure in a BTBR T+Itpr3tf/J mouse model (BTBR), a valid model that exhibits behavioral, electrical, and molecular features of autism, and compared this to the C57BL/6J wild-type control mouse. Using Western blot studies and high-resolution confocal microscopy in the prefrontal frontal cortex (PFC), our data indicate disrupted expression of different isoforms of the voltage-gated sodium channels (NaV) at the AIS, whereas other components of AIS such as ankyrin-G and fibroblast growth factor 14 (FGF14) and contactin-associated protein 1 (Caspr) in BTBR were comparable to those in wild-type control mice. A Western blot assay showed that BTBR mice exhibited a marked increase in different sodium channel isoforms in the PFC compared to wild-type mice. Our results provide potential evidence for previously undescribed mechanisms that may play a role in the pathogenesis of autistic-like phenotypes in BTBR mice.

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Neural circuits with long-distance axon tracts for determining functional connectivity

Cited by 15 publications

References 51 publications

An in vitro method to manipulate the direction and functional strength between neural populations

An in vitro method to manipulate the direction and functional strength between neural populations

Dissecting the mechanical behavior of neuronal microcompartments by combining magnetic tweezers and protein micropatterns

Changes in the Fluorescence Tracking of NaV1.6 Protein Expression in a BTBR T+Itpr3tf/J Autistic Mouse Model

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