Neural correlates of individual odor preference in Drosophila

Behavior varies even among genetically identical animals raised in the same environment. However, little is known about the circuit or anatomical underpinnings of this individuality. Drosophila olfaction is an ideal system for discovering the origins of behavioral individuality among genetically identical individuals. The fly olfactory circuit is well-characterized and stereotyped, yet stable idiosyncrasies in odor preference, neural coding, and neural wiring are present and may be relevant to behavior. Using paired behavior and two-photon imaging measurements, we show that individual odor preferences in odor-vs-air and odor-vs-odor assays are predicted by idiosyncratic calcium dynamics in Olfactory Receptor Neurons (ORNs) and Projection Neurons (PNs), respectively. This suggests that circuit variation at the sensory periphery determines individual odor preferences. Furthermore, paired behavior and immunohistochemistry measurements reveal that variation in ORN presynaptic density also predicts odor-vs-odor preference. This point in the olfactory circuit appears to be a locus of individuality where microscale variation gives rise to idiosyncratic behavior. To unify these results, we constructed a leaky-integrate-and-fire model of 3,062 neurons in the antennal lobe. In these simulations, stochastic fluctuations at the glomerular level, like those observed in our ORN immunohistochemistry, produce variation in PN calcium responses with the same structure as we observed experimentally, the very structure that predicts idiosyncratic behavior. Thus, our results demonstrate how minute physiological and structural variations in a neural circuit may produce individual behavior, even when genetics and environment are held constant.

In vivo coupling of dendritic complexity with presynaptic density in primary tauopathies

ABSTRACTUnderstanding the cellular underpinnings of neurodegeneration remains a challenge; loss of synapses and dendritic arborisation are characteristic and can be quantified in vivo, with [11C]UCB-J PET and MRI-based Orientation Dispersion Imaging (ODI), respectively. We aimed to assess how both measures are correlated, in 4R-tauopathies of Progressive Supranuclear Palsy (PSP-RS; n = 22) and amyloid-negative (determined by [11C]PiB PET) Corticobasal Degeneration (CBD; n =14), as neurodegenerative disease models, in this proof-of-concept study. Compared to controls (n = 27), PSP-RS and CBD patients had widespread reductions in cortical ODI, and [11C]UCB-J non-displaceable binding potential (BPND) in excess of atrophy. In PSP-RS and CBD separately, regional cortical ODI was significantly associated with [11C]UCB-J BPND in disease-associated regions (p < 0.05, FDR corrected). Our findings indicate that reductions in synaptic density and dendritic complexity in PSP-RS and CBD are more severe and extensive than atrophy. Furthermore, both measures are tightly coupled in vivo, furthering our understanding of the pathophysiology of neurodegeneration, and applicable to studies of early neurodegeneration with a safe and widely available MRI platform.

Intra-Amniotic LPS Induced Region-Specific Changes in Presynaptic Bouton Densities in the Ovine Fetal Brain

Rationale. Chorioamnionitis has been associated with increased risk for fetal brain damage. Although, it is now accepted that synaptic dysfunction might be responsible for functional deficits, synaptic densities/numbers after a fetal inflammatory challenge have not been studied in different regions yet. Therefore, we tested in this study the hypothesis that LPS-induced chorioamnionitis caused profound changes in synaptic densities in different regions of the fetal sheep brain.Material and Methods. Chorioamnionitis was induced by a 10 mg intra-amniotic LPS injection at two different exposure intervals. The fetal brain was studied at 125 days of gestation (term = 150 days) either 2 (LPS2D group) or 14 days (LPS14D group) after LPS or saline injection (control group). Synaptophysin immunohistochemistry was used to quantify the presynaptic density in layers 2-3 and 5-6 of the motor cortex, somatosensory cortex, entorhinal cortex, and piriforme cortex, in the nucleus caudatus and putamen and in CA1/2, CA3, and dentate gyrus of the hippocampus.Results. There was a significant reduction in presynaptic bouton densities in layers 2-3 and 5-6 of the motor cortex and in layers 2-3 of the entorhinal and the somatosensory cortex, in the nucleus caudate and putamen and the CA1/2 and CA3 of the hippocampus in the LPS2D compared to control animals. Only in the motor cortex and putamen, the presynaptic density was significantly decreased in the LPS14 D compared to the control group. No changes were found in the dentate gyrus of the hippocampus and the piriforme cortex.Conclusion. We demonstrated that LPS-induced chorioamnionitis caused a decreased density in presynaptic boutons in different areas in the fetal brain. These synaptic changes seemed to be region-specific, with some regions being more affected than others, and seemed to be transient in some regions.

Sex Differences in Presynaptic Density and Neurogenesis in Middle-Aged ApoE4 and ApoE Knockout Mice

Atherosclerosis and apolipoprotein E ε4 (APOE4) genotype are risk factors for Alzheimer’s disease (AD) and cardiovascular disease (CVD). Sex differences exist in prevalence and manifestation of both diseases. We investigated sex differences respective to aging, focusing on cognitive parameters in apoE4 and apoE knockout (ko) mouse models of AD and CVD. Presynaptic density and neurogenesis were investigated immunohistochemically in male and female apoE4, apoE ko, and wild-type mice. Middle-aged female apoE4 mice showed decreased presynaptic density in the inner molecular layer of the dentate gyrus of the hippocampus. Middle-aged female apoE ko mice showed a trend towards increased neurogenesis in the hippocampus compared with wild-type mice. No differences in these parameters could be observed in middle-aged male mice. Specific harmful interactions between apoE4 and estrogen could be responsible for decreased presynaptic density in female apoE4 mice. The trend of increased neurogenesis found in female apoE ko mice supports previous studies suggesting that temporarily increased amount of synaptic contacts and/or neurogenesis is a compensatory mechanism for synaptic failure. To our knowledge, no other studies investigating presynaptic density in aging female apoE4 or apoE ko mice are available. Sex-specific differences between APOE genotypes could account for some sex differences in AD and CVD.