Stimulus-Evoked Activity Modulation of In Vitro Engineered Cortical and Hippocampal Networks

Abstract

The delivery of electrical stimuli is crucial to shape the electrophysiological activity of neuronal populations and to appreciate the response of the different brain circuits involved. In the present work, we used dissociated cortical and hippocampal networks coupled to Micro-Electrode Arrays (MEAs) to investigate the features of their evoked response when a low-frequency (0.2 Hz) electrical stimulation protocol is delivered. In particular, cortical and hippocampal neurons were topologically organized to recreate interconnected sub-populations with a polydimethylsiloxane (PDMS) mask, which guaranteed the segregation of the cell bodies and the connections among the sub-regions through microchannels. We found that cortical assemblies were more reactive than hippocampal ones. Despite both configurations exhibiting a fast (<35 ms) response, this did not uniformly distribute over the MEA in the hippocampal networks. Moreover, the propagation of the stimuli-evoked activity within the networks showed a late (35–500 ms) response only in the cortical assemblies. The achieved results suggest the importance of the neuronal target when electrical stimulation experiments are performed. Not all neuronal types display the same response, and in light of transferring stimulation protocols to in vivo applications, it becomes fundamental to design realistic in vitro brain-on-a-chip devices to investigate the dynamical properties of complex neuronal circuits.

Neuromorphic-Based Neuroprostheses for Brain Rewiring: State-of-the-Art and Perspectives in Neuroengineering

“…Recently, the cortico-hippocampal circuit has been studied from both a functional and a structural point of view, pointing out the role of inhibitory connections during the development of the network in modulating the cortical dynamic [ 124 ]. In addition, these experimental models based on interacting neuronal populations allow us to perform experiments of electrical or chemical stimulation to quantify the role of the connections between the sub-assemblies and how different neuronal types respond to an external modulation [ 125 ]. The bimodular models were overcome in 2017 with an in vitro model where neurons extracted from the cortex, hippocampus, and amygdala were interconnected with the aim to understand the onset and the development of schizophrenia [ 126 ].…”

Spatial Computing in Modular Spiking Neural Networks with a Robotic Embodiment

“…Typically, modular networks include only two subnets, but the possibility of forming several interacting modules has already been reported [26][27][28]. In addition, it is worth mentioning that recently, to ensure heterogeneity, it has been proposed to use modules of neurons of different types within the same network, for example cortical and hippocampal [29] modules, which differ in neurodynamic properties [30].…”

Modularity and neuronal heterogeneity: Two properties that influence in vitro neuropharmacological experiments

“…Dissociated neuronal cultures coupled to Micro-Electrode Arrays (MEAs) are extensively used as in vitro model to study the mechanisms of the brain, such as the propagation of the signals ( Callegari et al, 2022 ), to understand the progression of diseases, and to test the neuroactive and neurotoxic properties of different compounds delivered to neuronal tissues ( Gramowski et al, 2000 ; Parviz and Gross, 2007 ). The first prototypes of MEAs developed by Gross (1979) were used as cell-based biosensors ( Gross et al, 1992 ).…”