Evidence That Separate Neural Circuits in the Nucleus Accumbens Encode Cocaine Versus “Natural” (Water and Food) Reward

Electrophysiological recording procedures were used to examine nucleus accumbens (Acb) cell firing in rats trained to press a lever on a multiple schedule [ fixed ratio (FR)1, FR1] for either two "natural" reinforcers (food and water), or a natural reinforcer and intravenous self-administration of cocaine. Of 180 cells recorded during water and food reinforcement (n = 13 rats), 77 neurons were classified as phasically active, exhibiting one of three well-defined types of patterned discharges relative to the reinforced-response (Carelli and Deadwyler, 1994). Of the 77 phasic cells, the majority (68%) showed similar types of patterned discharges across the two natural reinforcer conditions. In contrast, of 127 neurons recorded during water and cocaine reinforcement (n = 8 rats), only 5 of 60 phasically active cells (8%) exhibited similar types of patterned discharges relative to water- and cocaine-reinforced responding. The remaining 55 phasic cells (92%) displayed patterned discharges relative to the cocaine-reinforced response (n = 26 cells), or relative to the water-reinforced response (n = 29 cells), but not both. For some rats (n = 3), food was substituted for water in the task. Again, the majority of phasic neurons (13 of 14 cells, 93%) exhibited nonoverlapping firing patterns across the drug and natural reinforcer conditions. These findings indicate that in the well-trained animal, cocaine activates a neural circuit in the Acb that is largely separate from the circuit that processes information about food and water reward

Frequency selectivity in Old-World monkeys corroborates sharp cochlear tuning in humans

Frequency selectivity in the inner ear is fundamental to hearing and is traditionally thought to be similar across mammals. Although direct measurements are not possible in humans, estimates of frequency tuning based on noninvasive recordings of sound evoked from the cochlea (otoacoustic emissions) have suggested substantially sharper tuning in humans but remain controversial. We report measurements of frequency tuning in macaque monkeys, Old-World primates phylogenetically closer to humans than the laboratory animals often taken as models of human hearing (e.g., cats, guinea pigs, chinchillas). We find that measurements of tuning obtained directly from individual auditory-nerve fibers and indirectly using otoacoustic emissions both indicate that at characteristic frequencies above about 500 Hz, peripheral frequency selectivity in macaques is significantly sharper than in these common laboratory animals, matching that inferred for humans above 4–5 kHz. Compared with the macaque, the human otoacoustic estimates thus appear neither prohibitively sharp nor exceptional. Our results validate the use of otoacoustic emissions for noninvasive measurement of cochlear tuning and corroborate the finding of sharp tuning in humans. The results have important implications for understanding the mechanical and neural coding of sound in the human cochlea, and thus for developing strategies to compensate for the degradation of tuning in the hearing-impaired

FM Dye Photo-Oxidation as a Tool for Monitoring Membrane Recycling in Inner Hair Cells

Styryl (FM) dyes have been used for more than two decades to investigate exo- and endocytosis in conventional synapses. However, they are difficult to use in the inner hair cells of the auditory pathway (IHCs), as FM dyes appear to penetrate through mechanotransducer channels into the cytosol of IHCs, masking endocytotic uptake. To solve this problem we applied to IHCs the FM dye photo-oxidation technique, which renders the dyes into electron microscopy markers. Photo-oxidation allowed the unambiguous identification of labeled organelles, despite the presence of FM dye in the cytosol. This enabled us to describe the morphologies of several organelles that take up membrane in IHCs, both at rest and during stimulation. At rest, endosome-like organelles were detected in the region of the cuticular plate. Larger tubulo-cisternal organelles dominated the top and nuclear regions. Finally, the basal region, where the IHC active zones are located, contained few labeled organelles. Stimulation increased significantly membrane trafficking in the basal region, inducing the appearance of labeled vesicles and cistern-like organelles. The latter were replaced by small, synaptic-like vesicles during recovery after stimulation. In contrast, no changes in membrane trafficking were induced by stimulation in the cuticular plate region or in the top and nuclear regions. We conclude that synaptic vesicle recycling takes place mostly in the basal region of the IHCs. Other organelles participate in abundant constitutive membrane trafficking throughout the rest of the IHC volume.Open-Access-Publikationsfonds 2014peerReviewe