Conflicting views exist of how circuits of the antennal lobe, the insect equivalent of the olfactory bulb, translate input from olfactory receptor neurons (ORNs) into projection-neuron (PN) output. Synaptic connections between ORNs and PNs are one-to-one, yet PNs are more broadly tuned to odors than ORNs. The basis for this difference in receptive range remains unknown. Analyzing a Drosophila mutant lacking ORN input to one glomerulus, we show that some of the apparent complexity in the antennal lobe's output arises from lateral, interglomerular excitation of PNs. We describe a previously unidentified population of cholinergic local neurons (LNs) with multiglomerular processes. These excitatory LNs respond broadly to odors but exhibit little glomerular specificity in their synaptic output, suggesting that PNs are driven by a combination of glomerulus-specific ORN afferents and diffuse LN excitation. Lateral excitation may boost PN signals and enhance their transmission to third-order neurons in a mechanism akin to stochastic resonance.

Dopaminergic neurons are thought to drive learning by signaling changes in the expectations of salient events, such as rewards or punishments. Olfactory conditioning in Drosophila requires direct dopamine action on intrinsic mushroom body neurons, the likely storage sites of olfactory memories. Neither the cellular sources of the conditioning dopamine nor its precise postsynaptic targets are known. By optically controlling genetically circumscribed subsets of dopaminergic neurons in the behaving fly, we have mapped the origin of aversive reinforcement signals to the PPL1 cluster of 12 dopaminergic cells. PPL1 projections target restricted domains in the vertical lobes and heel of the mushroom body. Artificially evoked activity in a small number of identifiable cells thus suffices for programming behaviorally meaningful memories. The delineation of core reinforcement circuitry is an essential first step in dissecting the neural mechanisms that compute and represent valuations, store associations, and guide actions.

In the above article, Figure 2A is stated to summarize data from Figures 1A and 1B; however, we inadvertently displayed a plot of a different data set that was collected with a similar but slightly different experimental design. The data in Figures 1A and 1B are from an experiment in which one group of flies underwent mock conditioning and an independent group was conditioned with electric shock, whereas the data in Figure 2A were from an experiment in which the same population of flies sequentially underwent mock conditioning and actual conditioning.We provide here a corrected graph for Figure 2A plotting the data from Figure 1. The new plot does not affect the description of the results in the paper or the conclusions drawn. We apologize for any inconvenience caused by this error.

Pathological evidence suggests that alterations of the blood-brain barrier (BBB) may occur in association with human immunodeficiency virus (HIV) dementia (HIVD). Increased BBB permeability could contribute to the development of dementia by facilitating the entry of activated and infected monocytes, as well as potentially toxic serum proteins, into the central nervous system. One mechanism by which BBB permeability may be altered is through increased activity of select matrix metalloproteinases (MMPs). In the present study, we examined the possibility that MMPs that target critical BBB proteins, including laminin, entactin, and collagen type IV, are elevated in the cerebrospinal fluid (CSF) of patients with HIVD. We also examined the possibility that such MMPs could be produced by brain-derived cells, and that MMP production by these cells might be increased by tumor necrosis factor-␣, an inflammatory cytokine that is produced by HIV-infected monocytes/microglia and is elevated in HIVD. By using western blot and enzyme-linked immunosorbent assay, we observed that CSF levels of pro-MMP-2 and pro-MMP-7 were increased in association with HIVD. In addition, through the use of gelatin substrate zymography, a sensitive functional assay for MMP-2 and MMP-9, we observed that MMP-2 or pro-MMP-9 activity was more frequently detectable in the CSF of individuals with HIV dementia (9/16) than in the CSF from either nondemented seropositive (2/11) or seronegative (0/11) controls. Although the presence of MMPs in the serum could contribute to elevated levels in the CSF, we also show that brain-derived cells release MMP-2, 7, and 9, and that such release is increased after their stimulation with tumor necrosis factor-␣. Together, these results suggest that elevated CSF levels of select MMPs may reflect immune activation within the central nervous system. They also suggest that further studies may be warranted to determine whether these proteins may play a role in the development of symptomatic neurological disease.