An official website of the United States government
Neural network flexibility includes changes in neuronal participation between networks, such as the switching of neurons between single- and dual-network activity. We previously identified a neuron that is recruited to burst in time with an additional network via modulation of its intrinsic membrane properties, instead of being recruited synaptically into the second network. However, the modulated intrinsic properties were not determined. Here, we use small networks in the Jonah crab ( Cancer borealis) stomatogastric nervous system (STNS) to examine modulation of intrinsic properties underlying neuropeptide (Gly 1 -SIFamide)-elicited neuronal switching. The lateral posterior gastric neuron (LPG) switches from exclusive participation in the fast pyloric (∼1 Hz) network, due to electrical coupling, to dual-network activity that includes periodic escapes from the fast rhythm via intrinsically generated oscillations at the slower gastric mill network frequency (∼0.1 Hz). We isolated LPG from both networks by pharmacology and hyperpolarizing current injection. Gly 1 -SIFamide increased LPG intrinsic excitability and rebound from inhibition and decreased spike frequency adaptation, which can all contribute to intrinsic bursting. Using ion substitution and channel blockers, we found that a hyperpolarization-activated current, a persistent sodium current, and calcium or calcium-related current(s) appear to be primary contributors to Gly 1 -SIFamide-elicited LPG intrinsic bursting. However, this intrinsic bursting was more sensitive to blocking currents when LPG received rhythmic electrical coupling input from the fast network than in the isolated condition. Overall, a switch from single- to dual-network activity can involve modulation of multiple intrinsic properties, while synaptic input from a second network can shape the contributions of these properties. NEW & NOTEWORTHY Neuropeptide-elicited intrinsic bursting was recently determined to switch a neuron from single- to dual-network participation. Here we identified multiple intrinsic properties modulated in the dual-network state and candidate ion channels underlying the intrinsic bursting. Bursting at the second network frequency was more sensitive to blocking currents in the dual-network state than when neurons were synaptically isolated from their home network. Thus, synaptic input can shape the contributions of modulated intrinsic properties underlying dual-network activity.
more »
« less
Mathematical model of subthalamic nucleus neuron: Characteristic activity patterns and bifurcation analysis
The subthalamic nucleus (STN) has an important role in the pathophysiology of the basal ganglia in Parkinson's disease. The ability of STN cells to generate bursting rhythms under either transient or sustained hyperpolarization may underlie the excessively synchronous beta rhythms observed in Parkinson's disease. In this study, we developed a conductance-based single compartment model of an STN neuron, which is able to generate characteristic activity patterns observed in experiments including hyperpolarization-induced bursts and post-inhibitory rebound bursts. This study focused on the role of three currents in rhythm generation: T-type calcium (CaT) current, L-type calcium (CaL) current, and hyperpolarization-activated cyclic nucleotide-gated (HCN) current. To investigate the effects of these currents in rhythm generation, we performed a bifurcation analysis using slow variables in these currents. Bifurcation analysis showed that the HCN current promotes single-spike activity patterns rather than bursting in agreement with experimental results. It also showed that the CaT current is necessary for characteristic bursting activity patterns. In particular, the CaT current enables STN neurons to generate these activity patterns under hyperpolarizing stimuli. The CaL current enriches and reinforces these characteristic activity patterns. In hyperpolarization-induced bursts or post-inhibitory rebound bursts, the CaL current allows STN neurons to generate long bursting patterns. Thus, the bifurcation analysis explained the synergistic interaction of the CaT and CaL currents, which enables STN neurons to respond to hyperpolarizing stimuli in a salient way. The results of this study implicate the importance of CaT and CaL currents in the pathophysiology of the basal ganglia in Parkinson's disease.
more »
« less
- PAR ID:
- 10588487
- Publisher / Repository:
- American Institute of Physics
- Date Published:
- Journal Name:
- Chaos: An Interdisciplinary Journal of Nonlinear Science
- Volume:
- 31
- Issue:
- 11
- ISSN:
- 1054-1500
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Recordings from pre-Bötzinger complex neurons responsible for the inspiratory phase of the respiratory rhythm reveal a ramping burst pattern, starting around the time that the transition from expiration to inspiration begins, in which the spike rate gradually rises until a transition into a high-frequency burst occurs. The spike rate increase along the burst is accompanied by a gradual depolarization of the plateau potential that underlies the spikes. These effects may be functionally important for inducing the onset of inspiration and hence maintaining effective respiration; however, most mathematical models for inspiratory bursting do not capture this activity pattern. Here, we study how the modulation of spike height and afterhyperpolarization via the slow inactivation of an inward current can support various activity patterns including ramping bursts. We use dynamical systems methods designed for multiple timescale systems, such as bifurcation analysis based on timescale decomposition and averaging over fast oscillations, to generate an understanding of and predictions about the specific dynamic effects that lead to ramping bursts. We also analyze how transitions between ramping and other activity patterns may occur with parameter changes, which could be associated with experimental manipulations, environmental conditions, and/or development.more » « less
-
Linked rhythmic behaviors, such as respiration/locomotion or swallowing/chewing, often require coordination for proper function. Despite its prevalence, the cellular mechanisms controlling coordination of the underlying neural networks remain undetermined in most systems. We use the stomatogastric nervous system of the crabCancer borealisto investigate mechanisms of internetwork coordination, due to its small, well-characterized feeding-related networks (gastric mill [chewing, ∼0.1 Hz]; pyloric [filtering food, ∼1 Hz]). Here, we investigate coordination between these networks during the Gly1-SIFamide neuropeptide modulatory state. Gly1-SIFamide activates a unique triphasic gastric mill rhythm in which the typically pyloric-only LPG neuron generates dual pyloric-plus gastric mill-timed oscillations. Additionally, the pyloric rhythm exhibits shorter cycles during gastric mill rhythm-timed LPG bursts, and longer cycles during IC, or IC plus LG gastric mill neuron bursts. Photoinactivation revealed that LPG is necessary to shorten pyloric cycle period, likely through its rectified electrical coupling to pyloric pacemaker neurons. Hyperpolarizing current injections demonstrated that although LG bursting enables IC bursts, only gastric mill rhythm bursts in IC are necessary to prolong the pyloric cycle period. Surprisingly, LPG photoinactivation also eliminated prolonged pyloric cycles, without changing IC firing frequency or gastric mill burst duration, suggesting that pyloric cycles are prolonged via IC synaptic inhibition of LPG, which indirectly slows the pyloric pacemakers via electrical coupling. Thus, the same dual-network neuron directly conveys excitation from its endogenous bursting and indirectly funnels synaptic inhibition to enable one network to alternately decrease and increase the cycle period of a related network.more » « less
-
Abstract Square-wave bursting is an activity pattern common to a variety of neuronal and endocrine cell models that has been linked to central pattern generation for respiration and other physiological functions. Many of the reduced mathematical models that exhibit square-wave bursting yield transitions to an alternative pseudo-plateau bursting pattern with small parameter changes. This susceptibility to activity change could represent a problematic feature in settings where the release events triggered by spike production are necessary for function. In this work, we analyze how model bursting and other activity patterns vary with changes in a timescale associated with the conductance of a fast inward current. Specifically, using numerical simulations and dynamical systems methods, such as fast-slow decomposition and bifurcation and phase-plane analysis, we demonstrate and explain how the presence of a slow negative feedback associated with a gradual reduction of a fast inward current in these models helps to maintain the presence of spikes within the active phases of bursts. Therefore, although such a negative feedback is not necessary for burst production, we find that its presence generates a robustness that may be important for function.more » « less
-
Dominant neuroanatomical models hold that humans regulate their movements via loop-like cortico-subcortical networks, which include the subthalamic nucleus (STN), motor thalamus, and sensorimotor cortex (SMC). Inhibitory commands across these networks are purportedly sent via transient, burst-like signals in the β frequency (15–29 Hz). However, since human depth-recording studies are typically limited to one recording site, direct evidence for this proposition is hitherto lacking. Here, we present simultaneous multi-site recordings from SMC and either STN or motor thalamus in humans performing the stop-signal task. In line with their purported function as inhibitory signals, subcortical β-bursts were increased on successful stop-trials. STN bursts in particular were followed within 50 ms by increased β-bursting over SMC. Moreover, between-site comparisons (including in a patient with simultaneous recordings from SMC, thalamus, and STN) confirmed that β-bursts in STN temporally precede thalamic β-bursts. This highly unique set of recordings provides empirical evidence for the role of β-bursts in conveying inhibitory commands along long-proposed cortico-subcortical networks underlying movement regulation in humans.more » « less
