This Week in The Journal
Shaping Inhibition in Cortical Neurons
Voltage- and Site-Dependent Control of the Somatic Impact of Dendritic IPSPs
Stephen R. Williams and Greg J. Stuart
(see pages 7358-7367)
GABAergic neurons come in a variety of sizes and shapes, as do their postsynaptic responses, the IPSPs that are targeted to specific dendritic compartments. The amplitude and time course of IPSPs as well as their distribution along the dendrite determine how inhibition influences circuit behavior. In this issue, Williams and Stuart investigated the impact of IPSP location using triple somatic and dendritic recording in layer 5 cortical pyramidal cells. IPSPs were simulated as conductance sources of nonuniform shape using a "dynamic clamp." They found that interaction of IPSPs with a nonuniform distribution of ion channels provides voltage- and site-dependent control of inhibition. At depolarized membrane potentials (-50 mV), axosomatic "persistent" sodium current (INAP) increased the time course of IPSPs generated on proximal dendrites, whereas hyperpolarization-activated IH current on distal dendrites was responsible for the site-independent time course at more negative membrane potentials (-80 mV). The amplification of IPSP amplitude was also greater at -50 mV. The nonuniform localization of IH and INAP modulates GABAergic inhibition of axonal action potential firing at depolarized potentials, while at the same time preserving local synaptic integration along dendrites when the membrane potential is more hyperpolarized.
Laminating the Dentate Gyrus
Different Signals Control Laminar Specificity of Commissural and Entorhinal Fibers to the Dentate Gyrus
Shanting Zhao, Eckart Förster, Xuejun Chai, and Michael Frotscher
(see pages 7351-7357)
Both entorhinal afferents and commissural fibers of the hippocampus terminate in the molecular layer of the dentate gyrus, but are sharply segregated to the outer and innerlayers, respectively. Although the specific factors that create this crisp delineation remain unknown, candidate molecules include diffusible factors, membrane-bound proteins on both afferent and target neurons, and molecules of the extracellular matrix (ECM). In this week's Journal, Zhao et al. examine this problem by taking advantage of reeler mutant mice that have improperly positioned target granule cells. They cocultured brain slices from wild-type and reeler mice to establish that the entorhinal and commissural fibers use entirely different guiding factors. The results show that entorhinal afferents, but not commissural fibers, rely on the ECM molecule hyaluronic acid for proper termination in the laminated dentate gyrus. Commissural fibers, incontrast, seem to be guided by the position, or in the case of reeler mice, by the malposition of their target granule cells.
Abstinence and the Accumbens
Persistent Cue-Evoked Activity of Accumbens Neurons after Prolonged Abstinence from Self-Administered Cocaine
Udi E. Ghitza, Anthony T. Fabbricatore, Volodymyr Prokopenko, Anthony P. Pawlak, and Mark O. West
(see pages 7239-7245)
Environmental cues that are associated with cocaine use by an addict, even long after stopping drug use, can trigger a relapse into addictive behavior. Similarly, rats trained to self-administer cocaine will resume drug-seeking behavior in response to stimuli that signal drug availability even after long drug-free periods. The neuronal circuitry of the mesocorticolimbic dopamine system controls this relapse behavior, but the specific neurons that are activated by these cues are not known. Now Ghitza et al., using single-unit recording in vivo, report that the neurons of the shell, but not the core, of the nucleus accumbens (NAcc) are responsive to these stimuli. Rats trained to self-administer cocaine were presented with a persistent "discriminative stimulus" (SD) tone during drug delivery. After several weeks of abstinence, the rats underwent an extinction process. Presentation of the SD tone elicited drug-seeking behavior and was preceded by increased activity in shell neurons. The core neurons, in contrast, did not seem to distinguish between the SD tone and a neutral tone. The results suggest that neural activity in the NAcc shell may be a cellular correlate of relapse in drug abusers even after long periods of abstinence.