Using a Hybrid Neural System to Reveal Regulation of Neuronal Network Activity by an Intrinsic Current

Abstract

The generation of rhythmic patterns by neuronal networks is a complex phenomenon, relying on the interaction of numerous intrinsic and synaptic currents, as well as modulatory agents. To investigate the functional contribution of an individual ionic current to rhythmic pattern generation in a network, we constructed a hybrid system composed of a silicon model neuron and a heart interneuron from the heartbeat timing network of the medicinal leech. When the model neuron and a heart interneuron are connected by inhibitory synapses, they produce rhythmic activity similar to that observed in the heartbeat network. We focused our studies on investigating the functional role of the hyperpolarization-activated inward current (I h ) on the rhythmic bursts produced by the network. By introducing changes in both the model and the heart interneuron, we showed that I h determines both the period of rhythmic bursts and the balance of activity between the two sides of the network, because the amount and the activation/deactivation time constant of I h determines the length of time that a neuron spends in the inhibited phase of its burst cycle. Moreover, we demonstrated that the model neuron is an effective replacement for a heart interneuron and that changes made in the model can accurately mimic similar changes made in the living system. Finally, we used a previously developed mathematical model (Hill et al. 2001) of two mutually inhibitory interneurons to corroborate these findings. Our results demonstrated that this hybrid system technique is advantageous for investigating neuronal properties that are inaccessible with traditional techniques.

Control of neuronal firing by dynamic parallel fiber feedback:implications for electrosensory reafference suppression

“…Therefore, to assess their impact on post-synaptic neuron firing we used a hybrid experimental-modeling approach in a brain slice preparation, similar in nature to previous studies (e.g. Sharp et al, 1993;Sorensen et al, 2004;Prinz et al, 2004). This so-called 'dynamic clamp' allows the delivery of an intracellular current stimulus that mimics any voltage-dependent or synaptic conductance, given that it can be described by a computer model.…”

Inferring and quantifying the role of an intrinsic current in a mechanism for a half-center bursting oscillation

“…This model uses a half-center oscillator (HCO) architecture of two inhibitory interneurons. Previous investigations of this CPG through modeling studies (e.g., [5]) and experimental studies (e.g., [16]) have yielded possible mechanisms involving I h in broad natural language terms. Here, our primary goal was to take advantage of an existing model and previous studies of its properties as an expository case study: we seek to validate the previous natural language descriptions through a more formal approach, and improve upon their clarity, robustness, and specificity.…”

“…Previous studies of this HCO model and electrophysiological studies of the leech heartbeat have addressed fundamental questions about the mechanism of bursting [4,5,[13][14][15][16][17]. Regarding I h specifically, these questions can be summarized in terms of roles: R1: What role does I h have in the existence of a stable HCO rhythm?…”

“…From this, we hypothesize different roles for I h in each regime, and explore the replacement of I h in one cell of the HCO with a simple but functionally equivalent behavior for each regime. We will reduce only one neuron of the coupled pair, in a similar fashion to the neural-silicon circuit of Sorensen et al [16]. The purpose of this is to use the unreduced neuron as a reference, so that the quality of a reduction in the other neuron can be measured by the degree of symmetry preservation in the coupled system.…”

“…Broadly speaking, I h deactivates during B and activates during I, but its influence peaks in the middle of I, approximately 1s in advance of the onset of B for the canonical parameter values. We will explore whether this is important mechanistically, although it is already known from varying τ h that the exact relative position of the peak in I is not crucial to the mechanism of transition to B [16].…”