Active dendrites enhance neuronal dynamic range

Since the first experimental evidences of active conductances in dendrites, most neurons have been shown to exhibit dendritic excitability through the expression of a variety of voltage-gated ion channels. However, despite experimental and theoretical efforts undertaken in the last decades, the role of this excitability for some kind of dendritic computation has remained elusive. Here we show that, owing to very general properties of excitable media, the average output of a model of active dendritic trees is a highly non-linear function of their afferent rate, attaining extremely large dynamic ranges (above 50 dB). Moreover, the model yields double-sigmoid response functions as experimentally observed in retinal ganglion cells. We claim that enhancement of dynamic range is the primary functional role of active dendritic conductances. We predict that neurons with larger dendritic trees should have larger dynamic range and that blocking of active conductances should lead to a decrease of dynamic range.Comment: 20 pages, 6 figure

Controlled dosing of nicotine via an I ntranasal N icotine A erosol D elivery D evice (INADD)

The present report describes an I ntranasal N icotine A erosol D elivery D evice (INADD) employing an artist's airbrush as aerosolizer and precise, electromechanical control of spray duration. It was designed for the administration of controlled doses of nicotine in a laboratory setting and has been used successfully in over 30 smokers and nonsmokers of both genders. In the present study, nicotine was administered to 12 male smokers at three different doses (0.05 mg, 1.00 mg, and 2.00 mg), and at the same dose (1 mg) on three different occasions. The low dose produced a minimal change in plasma nicotine, while the high dose produced a peak increment of around 16 ng/ml. The medium dose reliably produced a peak increment of around 8–9 ng/ml on all three occasions. Nicotine in plasma showed a sharp rise followed by a slower decline, mimicking the pattern associated with cigarette smoking. Physiological and biochemical responses showed significant dose-response relationships. Subjective reports suggested that aerosol dosing was somewhat aversive, but it is unclear whether this effect is intrinsic to the method or due to other factors. The device described in this report answers the need for a safe and easy means of controlling nicotine dose. Moreover, since nicotine administration via aerosol is novel for both smokers and non-smokers, minimizing the contributions of behavioral tolerance and habituation to the dosing vehicle, it lends itself to the comparison of the pharmacological effects of nicotine between experienced and naive subjects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46339/1/213_2005_Article_BF02247431.pd

Robustness of Learning That Is Based on Covariance-Driven Synaptic Plasticity

It is widely believed that learning is due, at least in part, to long-lasting modifications of the strengths of synapses in the brain. Theoretical studies have shown that a family of synaptic plasticity rules, in which synaptic changes are driven by covariance, is particularly useful for many forms of learning, including associative memory, gradient estimation, and operant conditioning. Covariance-based plasticity is inherently sensitive. Even a slight mistuning of the parameters of a covariance-based plasticity rule is likely to result in substantial changes in synaptic efficacies. Therefore, the biological relevance of covariance-based plasticity models is questionable. Here, we study the effects of mistuning parameters of the plasticity rule in a decision making model in which synaptic plasticity is driven by the covariance of reward and neural activity. An exact covariance plasticity rule yields Herrnstein's matching law. We show that although the effect of slight mistuning of the plasticity rule on the synaptic efficacies is large, the behavioral effect is small. Thus, matching behavior is robust to mistuning of the parameters of the covariance-based plasticity rule. Furthermore, the mistuned covariance rule results in undermatching, which is consistent with experimentally observed behavior. These results substantiate the hypothesis that approximate covariance-based synaptic plasticity underlies operant conditioning. However, we show that the mistuning of the mean subtraction makes behavior sensitive to the mistuning of the properties of the decision making network. Thus, there is a tradeoff between the robustness of matching behavior to changes in the plasticity rule and its robustness to changes in the properties of the decision making network

The capabilities and limitations of conductance-based compartmental neuron models with reduced branched or unbranched morphologies and active dendrites

Conductance-based neuron models are frequently employed to study the dynamics of biological neural networks. For speed and ease of use, these models are often reduced in morphological complexity. Simplified dendritic branching structures may process inputs differently than full branching structures, however, and could thereby fail to reproduce important aspects of biological neural processing. It is not yet well understood which processing capabilities require detailed branching structures. Therefore, we analyzed the processing capabilities of full or partially branched reduced models. These models were created by collapsing the dendritic tree of a full morphological model of a globus pallidus (GP) neuron while preserving its total surface area and electrotonic length, as well as its passive and active parameters. Dendritic trees were either collapsed into single cables (unbranched models) or the full complement of branch points was preserved (branched models). Both reduction strategies allowed us to compare dynamics between all models using the same channel density settings. Full model responses to somatic inputs were generally preserved by both types of reduced model while dendritic input responses could be more closely preserved by branched than unbranched reduced models. However, features strongly influenced by local dendritic input resistance, such as active dendritic sodium spike generation and propagation, could not be accurately reproduced by any reduced model. Based on our analyses, we suggest that there are intrinsic differences in processing capabilities between unbranched and branched models. We also indicate suitable applications for different levels of reduction, including fast searches of full model parameter space

Dendritic Spike Saturation of Endogenous Calcium Buffer and Induction of Postsynaptic Cerebellar LTP

The architecture of parallel fiber axons contacting cerebellar Purkinje neurons retains spatial information over long distances. Parallel fiber synapses can trigger local dendritic calcium spikes, but whether and how this calcium signal leads to plastic changes that decode the parallel fiber input organization is unknown. By combining voltage and calcium imaging, we show that calcium signals, elicited by parallel fiber stimulation and mediated by voltage-gated calcium channels, increase non-linearly during high-frequency bursts of electrically constant calcium spikes, because they locally and transiently saturate the endogenous buffer. We demonstrate that these non-linear calcium signals, independently of NMDA or metabotropic glutamate receptor activation, can induce parallel fiber long-term potentiation. Two-photon imaging in coronal slices revealed that calcium signals inducing long-term potentiation can be observed by stimulating either the parallel fiber or the ascending fiber pathway. We propose that local dendritic calcium spikes, evoked by synaptic potentials, provide a unique mechanism to spatially decode parallel fiber signals into cerebellar circuitry changes

Spatially distributed dendritic resonance selectively filters synaptic input

© 2014 Laudanski et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.An important task performed by a neuron is the selection of relevant inputs from among thousands of synapses impinging on the dendritic tree. Synaptic plasticity enables this by strenghtening a subset of synapses that are, presumably, functionally relevant to the neuron. A different selection mechanism exploits the resonance of the dendritic membranes to preferentially filter synaptic inputs based on their temporal rates. A widely held view is that a neuron has one resonant frequency and thus can pass through one rate. Here we demonstrate through mathematical analyses and numerical simulations that dendritic resonance is inevitably a spatially distributed property; and therefore the resonance frequency varies along the dendrites, and thus endows neurons with a powerful spatiotemporal selection mechanism that is sensitive both to the dendritic location and the temporal structure of the incoming synaptic inputs.Peer reviewe

Biphasic Synaptic Ca Influx Arising from Compartmentalized Electrical Signals in Dendritic Spines

Dendritic spines compartmentalize synaptically-evoked biochemical signals. The authors show that electrical compartmentalization provided by a spine endows the associated synapse with additional modes of calcium signaling by shaping the kinetics of synaptic calcium currents

Enhancement Effects of Martentoxin on Glioma BK Channel and BK Channel (α+β1) Subtypes

BACKGROUND: BK channels are usually activated by membrane depolarization and cytoplasmic Ca(2+). Especially,the activity of BK channel (α+β4) can be modulated by martentoxin, a 37 residues peptide, with Ca(2+)-dependent manner. gBK channel (glioma BK channel) and BK channel (α+β1) possessed higher Ca(2+) sensitivity than other known BK channel subtypes. METHODOLOGY AND PRINCIPAL FINDINGS: The present study investigated the modulatory characteristics of martentoxin on these two BK channel subtypes by electrophysiological recordings, cell proliferation and Ca(2+) imaging. In the presence of cytoplasmic Ca(2+), martentoxin could enhance the activities of both gBK and BK channel (α+β1) subtypes in dose-dependent manner with EC(50) of 46.7 nM and 495 nM respectively, while not shift the steady-state activation of these channels. The enhancement ratio of martentoxin on gBK and BK channel (α+β1) was unrelated to the quantitative change of cytoplasmic Ca(2+) concentrations though the interaction between martentoxin and BK channel (α+β1) was accelerated under higher cytoplasmic Ca(2+). The selective BK pore blocker iberiotoxin could fully abolish the enhancement of these two BK subtypes induced by martentoxin, suggesting that the auxiliary β subunit might contribute to the docking for martentoxin. However, in the absence of cytoplasmic Ca(2+), the activity of gBK channel would be surprisingly inhibited by martentoxin while BK channel (α+β1) couldn't be affected by the toxin. CONCLUSIONS AND SIGNIFICANCE: Thus, the results shown here provide the novel evidence that martentoxin could increase the two Ca(2+)-hypersensitive BK channel subtypes activities in a new manner and indicate that β subunit of these BK channels plays a vital role in this enhancement by martentoxin