Hodgkin–Huxley Model of Backpropagating Spikes
Yuguo Yu, Yousheng Shu, and David A. McCormick
(see pages 7260–7272)
Axon potentials recorded in somata of pyramidal neurons in vivo have a fast rising phase and variable threshold, contrary to predictions of the Hodgkin–Huxley model. Some have suggested that this difference is due to cooperativity among sodium channels, resulting in many channels opening simultaneously. Yu et al. now show that the shape and threshold variability of somatic action potentials can be explained by the fact that spikes backpropagate to the soma from their initiation point, ∼40 μm along the axon. Simultaneous intracellular recordings from somata and axons in cortical slices revealed that the shape and threshold variability of spikes at the spike-initiating zone were consistent with predictions of the Hodgkin–Huxley model. Computer simulations confirmed that the rise times of spikes in the soma were influenced by backpropagation, and that threshold variability resulted from differences in membrane potential in the soma and axon initial segment at the time of spike initiation.
SCLIP Role in Purkinje Cell Dendritogenesis
Fabienne E. Poulain, Stéphanie Chauvin, Rosine Wehrlé, Mathieu Desclaux, Jacques Mallet, Guilan Vodjdani, Isabelle Dusart, and André Sobel
(see pages 7387–7398)
Purkinje cells develop highly branched dendritic arbors that receive tens of thousands of synaptic inputs. Poulain et al. report this week that SCLIP, a member of the stathmin family of microtubule-destabilizing proteins, is important in Purkinje cell dendritogenesis. In the developing cerebellum, SCLIP was expressed primarily in Purkinje cells, became concentrated in dendrites as they formed, and decreased when the dendritic arbor was fully formed. The expression was concentrated in the Golgi apparatus and other vesicular structures. Overexpression of SCLIP in postnatal organotypic cerebellar cultures accelerated dendritic development and increased the number and branching of primary dendrites. Conversely, early knockdown of SCLIP via RNA inhibition inhibited the initial formation of dendrites, and later knockdown inhibited growth and branching of nascent dendrites. Importantly, neighboring Purkinje cells that were not transfected with interfering RNAs developed normally, indicating that SCLIP affects dendritogenesis only in the cell in which it is expressed.
Stress and Cannabinoids
Silvia Rossi, Valentina De Chiara, Alessandra Musella, Hajime Kusayanagi, Giorgia Mataluni, Giorgio Bernardi, Alessandro Usiello, and Diego Centonze
(see pages 7284–7292)
The relationship between stress and the endocannabinoid system are complex, and activation of cannabinoid receptors can have diverse and apparently contradictory effects on the stress response. This complexity is further demonstrated this week by Rossi et al., who show that stress has different effects on GABAergic and glutamatergic transmission in the striatum, a brain area that has high levels of cannabinoid receptors and is important in stress responses. Mice were subjected daily to an aggressive male to induce social stress, and the effects of exogenous and endogenous cannabinoids were measured in corticostriatal slice cultures. Stress exposure eliminated the reductions in GABAergic IPSC frequency and amplitude that are normally produced by cannabinoids. In contrast, stress did not alter cannabinoid-mediated reduction in glutamatergic EPSC frequency and amplitude. Providing mice with rewards (exercise, sugar, or cocaine) after social stress eliminated the effects of stress on cannabinoid modulation of GABAergic transmission.
Neurobiology of Disease
Voltage-Gated Sodium Channel Mutations in Migraine
Sandrine Cestèle, Paolo Scalmani, Raffaella Rusconi, Benedetta Terragni, Silvana Franceschetti, and Massimo Mantegazza
(see pages 7273–7283)
Different mutations in the neuronal voltage-gated sodium channel (Nav1.1) cause familial hemiplegic migraine (FHM) or epilepsy. To help differentiate the physiological bases of these diseases, Cestèle et al. expressed human Nav1.1 channels bearing the FHM type 3 mutation (which results in an amino acid substitution in the inactivation gate) in a non-neural cell line and in cultured neocortical neurons. The electrophysiological properties of the mutant channel were consistent with it conferring a limited hyperexcitability on neurons. Compared to wild type, mutated channels had a positive shift in the voltage dependence of inactivation, reduced maximum current density, and faster inactivation. Some of these properties are expected to produce hyperexcitability, and others should favor hypoexcitability. Mutant channels appeared able to sustain high-frequency firing better than wild-type channels, but this ability was limited and disappeared after sustained depolarization. This limited hyperexcitability may distinguish migraine and epilepsy mutations.