No abstract

The lateral-line system is common to most aquatic organisms. It plays an important role in behaviours involving detection of other animals and obstacles. In gnathostome fishes, these behaviours appear to be dependent on an efferent inhibitory system that filters out stimuli caused by the animal’s own movement. Sea lampreys ( Petromyzon marinus L., 1758), the most basal extant vertebrate, possess a functional lateral-line system. Yet they completely lack the inhibitory efferent system. Thus, they may use the lateral line to sense their own swimming movements, helping to stabilize swimming. To test this hypothesis, we first investigated the kinematics of free-swimming lampreys. In an intact tethered preparation, we then generated undualatory body motions of comparable amplitude and frequency to swimming, while monitoring the evoked responses of the posterior lateral-line nerve. Last, we tested the effect of eliminating lateral-line inputs by cobalt treatment. In the tethered preparation, we recorded distinctive and consistent activity in the lateral-line nerve that was strongly dependent on characteristics of the motion. We found that distinct characteristics of the rhythmic movements are encoded in the temporal characteristics of the response. Swimming kinematics of cobalt-treated animals differed from controls, suggesting a complex, yet necessary role of the lateral-line system in closed-loop control of swimming.

Genetically modified mice have provided insights into the progression and pathology of Alzheimer’s disease (AD). Here, we have examined two mouse models of AD: the rTg4510 mouse, which overexpresses mutant human Tau gene, and the APP/PS1 mouse, which overexpresses mutant human genes for amyloid precursor protein and presenilin 1. Both models exhibit deficits in hippocampal function, but comparative analyses of these deficits are sparse. We used extracellular field potential recordings in hippocampal slices to study basal synaptic transmission (BST), paired-pulse facilitation (PPF), and long-term potentiation (LTP) at the Schaffer collateral-CA1 pyramidal cell synapses in both models. We found that 6-7, but not 2-3-month-old rTg4510 mice exhibited reduced pre-synaptic activation (fiber volley (FV) amplitude, ∼50%) and field excitatory post-synaptic potential (fEPSP) slope (∼40%) compared to wild-type controls. In contrast to previous reports, BST, when controlled for FV amplitude, was not altered in rTg4510. APP/PS1 mice (2-3 mo and 8-10 mo) had unchanged FV amplitude compared to wild-type controls, while fEPSP slope was reduced by ∼34% in older mice, indicating a deficit in BST. PPF was unchanged in 8–10-month-old APP/PS1 mice, but was reduced in 6-7-month-old rTg4510 mice. LTP was reduced only in older rTg4510 and APP/PS1 mice. Our data suggest that BST deficits appear earlier in APP/PS1 than in rTg4510, which exhibited no BST deficits at the ages tested. However, FV and synaptic plasticity deficits developed earlier in rTg4510. These findings highlight fundamental differences in the progression of synaptic pathology in two genetically distinct models of AD.

Background Huntington's disease (HD) is caused by a CAG repeat expansion in the huntingtin gene. This mutation leads to progressive dysfunction that is largely attributable to dysfunction of the striatum. The earliest signs of striatal pathology in HD are found in indirect pathway gamma‐Aminobutyric acid (GABA)‐ergic spiny projection neurons that innervate the external segment of the globus pallidus (GPe). What is less clear is whether the synaptic coupling of spiny projection neurons with GPe neurons changes in HD. Objectives The principal goal of this study was to determine whether striatopallidal synaptic transmission was altered in 2 mouse models of HD. Methods Striatopallidal synaptic transmission was studied using electrophysiological and optogenetic approaches in ex vivo brain slices from 2 HD models: Q175 heterozygous (het) and R6/2 mice. Results Striatopallidal synaptic transmission increased in strength with the progression of behavioral deficits in Q175 and R6/2 mice. The alteration in synaptic transmission was evident in both prototypical and arkypallidal GPe neurons. This change did not appear attributable to an increase in the probability of GABA release but, rather, to an enhancement in the postsynaptic response to GABA released at synaptic sites. This alteration significantly increased the ability of striatopallidal axon terminals to pause ongoing GPe activity. Conclusions In 2 mouse models of HD, striatopallidal synaptic transmission increased in parallel with the progression of behavioral deficits. This adaptation could compensate in part for the concomitant deficit in the ability of corticostriatal signals to activate spiny projection neurons and pause GPe activity. © 2019 International Parkinson and Movement Disorder Society