Many neurons possess dendrites enriched with sodium channels and are capable of generating action potentials. However, the role of dendritic sodium spikes remain unclear. Here, we study computational models of neurons to investigate the functional effects of dendritic spikes. In agreement with previous studies, we found that point neurons or neurons with passive dendrites increase their somatic firing rate in response to the correlation of synaptic bombardment for a wide range of input conditions, i.e. input firing rates, synaptic conductances, or refractory periods. However, neurons with active dendrites show the opposite behavior: for a wide range of conditions the firing rate decreases as a function of correlation. We found this property in three types of models of dendritic excitability: a Hodgkin-Huxley model of dendritic spikes, a model with integrate and fire dendrites, and a discrete-state dendritic model. We conclude that fast dendritic spikes confer much broader computational properties to neurons, sometimes opposite to that of point neurons.
Dopamine (DA) neurons of the ventrolateral periaqueductal gray (vlPAG) and dorsal raphe nucleus (DRN) fire spontaneous action potentials (APs) at slow, regular patterns in vitro but a detailed account of their intrinsic membrane properties responsible for spontaneous firing is currently lacking. To resolve this, we performed a voltage-clamp electrophysiological study in brain slices to describe their major ionic currents and then constructed a computer model and used simulations to understand the mechanisms behind autorhythmicity in silico. We found that vlPAG/DRN DA neurons exhibit a number of voltage-dependent currents activating in the subthreshold range including, a hyperpolarization-activated cation current (IH), a transient, A-type, potassium current (IA), a background, 'persistent' (INaP) sodium current and a transient, low voltage activated (LVA) calcium current (ICaLVA). Brain slice pharmacology, in good agreement with computer simulations, showed that spontaneous firing occurred independently of IH, IA or calcium currents. In contrast, when blocking sodium currents, spontaneous firing ceased and a stable, non-oscillating membrane potential below AP threshold was attained. Using the DA neuron model we further show that calcium currents exhibit little activation (compared to sodium) during the interspike interval (ISI) repolarization while, any individual potassium current alone, whose blockade positively modulated AP firing frequency, is not required for spontaneous firing. Instead, blockade of a number of potassium currents simultaneously is necessary to eliminate autorhythmicity. Repolarization during ISI is mediated initially via the deactivation of the delayed rectifier potassium current, while a sodium background 'persistent' current is essentially indispensable for autorhythmicity by driving repolarization towards AP threshold.
Journal Of Computational Neuroscience [J Comput Neurosci] 2017 Aug; Vol. 43 (1), pp. 93-106. Date of Electronic Publication: 2017 Jun 01.
Humans, Motor Neurons, Feedback, Models, Neurological, Motor Cortex physiology, Movement, and Neurons physiology
Primary motor cortex (M1) neurons are tuned in response to several parameters related to motor control, and it was recently reported that M1 is important in feedback control. However, it remains unclear how M1 neurons encode information to control the musculoskeletal system. In this study, we examined the underlying computational mechanisms of M1 based on optimal feedback control (OFC) theory, which is a plausible hypothesis for neuromotor control. We modelled an isometric torque production task that required joint torque to be regulated and maintained at desired levels in a musculoskeletal system physically constrained by muscles, which act by pulling rather than pushing. Then, a feedback controller was computed using an optimisation approach under the constraint. In the presence of neuromotor noise, known as signal-dependent noise, the sensory feedback gain is tuned to an extrinsic motor output, such as the hand force, like a population response of M1 neurons. Moreover, a distribution of the preferred directions (PDs) of M1 neurons can be predicted via feedback gain. Therefore, we suggest that neural activity in M1 is optimised for the musculoskeletal system. Furthermore, if the feedback controller is represented in M1, OFC can describe multiple representations of M1, including not only the distribution of PDs but also the response of the neuronal population.
Journal Of Computational Neuroscience [J Comput Neurosci] 2016 Apr; Vol. 40 (2), pp. 231-45. Date of Electronic Publication: 2016 Feb 22.
Action Potentials physiology, Animals, Electric Stimulation, Humans, Neural Conduction drug effects, Neural Conduction physiology, Neurons classification, Patch-Clamp Techniques, Periodicity, Potassium metabolism, Action Potentials drug effects, Extracellular Fluid metabolism, Medulla Oblongata cytology, Models, Neurological, Neurons physiology, and Potassium pharmacology
There are many types of neurons that intrinsically generate rhythmic bursting activity, even when isolated, and these neurons underlie several specific motor behaviors. Rhythmic neurons that drive the inspiratory phase of respiration are located in the medullary pre-Bötzinger Complex (pre-BötC). However, it is not known if their rhythmic bursting is the result of intrinsic mechanisms or synaptic interactions. In many cases, for bursting to occur, the excitability of these neurons needs to be elevated. This excitation is provided in vitro (e.g. in slices), by increasing extracellular potassium concentration (K out) well beyond physiologic levels. Elevated K out shifts the reversal potentials for all potassium currents including the potassium component of leakage to higher values. However, how an increase in K out , and the resultant changes in potassium currents, induce bursting activity, have yet to be established. Moreover, it is not known if the endogenous bursting induced in vitro is representative of neural behavior in vivo. Our modeling study examines the interplay between K out, excitability, and selected currents, as they relate to endogenous rhythmic bursting. Starting with a Hodgkin-Huxley formalization of a pre-BötC neuron, a potassium ion component was incorporated into the leakage current, and model behaviors were investigated at varying concentrations of K out. Our simulations show that endogenous bursting activity, evoked in vitro by elevation of K out , is the result of a specific relationship between the leakage and voltage-dependent, delayed rectifier potassium currents, which may not be observed at physiological levels of extracellular potassium.