Sensory-Evoked Spiking Behavior Emerges via an Experience-Dependent Plasticity Mechanism

van Rheede JJ, Richards BA, Akerman CJ

Neuron 2015 Sep;87(5):1050-62

PMID: 26335647


The ability to generate action potentials (spikes) in response to synaptic input determines whether a neuron participates in information processing. How a developing neuron becomes an active participant in a circuit or whether this process is activity dependent is not known, especially as spike-dependent plasticity mechanisms would not be available to non-spiking neurons. Here we use the optic tectum of awake Xenopus laevis tadpoles to determine how a neuron becomes able to generate sensory-driven spikes inĀ vivo. At the onset of vision, many tectal neurons do not exhibit visual spiking behavior, despite being intrinsically excitable and receiving visuotopically organized synaptic inputs. However, a brief period of visual stimulation can drive these neurons to start generating stimulus-driven spikes. This conversion relies upon a selective increase inĀ glutamatergic input and requires depolarizing GABAergic transmission and NMDA receptor activation. This permissive form of experience-dependent plasticity enables a neuron to start contributing to circuit function.

A central role of the BK potassium channel in behavioral responses to ethanol in C. elegans

Davies AG, Pierce-Shimomura JT, Kim H, VanHoven MK, Thiele TR, Bonci A, Bargmann CI, McIntire SL

Cell 2003 Dec;115(6):655-66

PMID: 14675531


The activities of many neuronal proteins are modulated by ethanol, but the fundamental mechanisms underlying behavioral effects of ethanol remain unclear. To identify mechanisms responsible for intoxication, we screened for Caenorhabditis elegans mutants with altered behavioral responses to ethanol. We found that slo-1 mutants, which were previously recognized as having slightly uncoordinated movement, are highly resistant to ethanol in two behavioral assays. Numerous loss-of-function slo-1 alleles emerged from our screens, indicating that slo-1 has a central role in ethanol responses. slo-1 encodes the BK potassium channel. Electrophysiological analysis shows that ethanol activates the channel in vivo, which would inhibit neuronal activity. Moreover, behaviors of slo-1 gain-of-function mutants resemble those of ethanol-intoxicated animals. These results demonstrate that selective activation of BK channels is responsible for acute intoxicating effects of ethanol in C. elegans. BK channel activation may explain a variety of behavioral responses to ethanol in invertebrate and vertebrate systems.

Natural variation in the npr-1 gene modifies ethanol responses of wild strains of C. elegans

Davies AG, Bettinger JC, Thiele TR, Judy ME, McIntire SL

Neuron 2004 Jun;42(5):731-43

PMID: 15182714


Variation in the acute response to ethanol between individuals has a significant impact on determining susceptibility to alcoholism. The degree to which genetics contributes to this variation is of great interest. Here we show that allelic variation that alters the functional level of NPR-1, a neuropeptide Y (NPY) receptor-like protein, can account for natural variation in the acute response to ethanol in wild strains of Caenorhabditis elegans. NPR-1 negatively regulates the development of acute tolerance to ethanol, a neuroadaptive process that compensates for effects of ethanol. Furthermore, dynamic changes in the NPR-1 pathway provide a mechanism for ethanol tolerance in C. elegans. This suggests an explanation for the conserved function of NPY-related pathways in ethanol responses across diverse species. Moreover, these data indicate that genetic variation in the level of NPR-1 function determines much of the phenotypic variation in adaptive behavioral responses to ethanol that are observed in natural populations.