Excitability and Synaptic Alterations in the Cerebellum of APP/PS1 Mice

In Alzheimer's disease (AD), the severity of cognitive symptoms is better correlated with the levels of soluble amyloid-beta (Aβ) rather than with the deposition of fibrillar Aβ in amyloid plaques. In APP/PS1 mice, a murine model of AD, at 8 months of age the cerebellum is devoid of fibrillar Aβ, but dosage of soluble Aβ1–42, the form which is more prone to aggregation, showed higher levels in this structure than in the forebrain. Aim of this study was to investigate the alterations of intrinsic membrane properties and of synaptic inputs in Purkinje cells (PCs) of the cerebellum, where only soluble Aβ is present. PCs were recorded by whole-cell patch-clamp in cerebellar slices from wild-type and APP/PS1 mice. In APP/PS1 PCs, evoked action potential discharge showed enhanced frequency adaptation and larger afterhyperpolarizations, indicating a reduction of the intrinsic membrane excitability. In the miniature GABAergic postsynaptic currents, the largest events were absent in APP/PS1 mice and the interspike intervals distribution was shifted to the left, but the mean amplitude and frequency were normal. The ryanodine-sensitive multivescicular release was not altered and the postsynaptic responsiveness to a GABAA agonist was intact. Climbing fiber postsynaptic currents were normal but their short-term plasticity was reduced in a time window of 100–800 ms. Parallel fiber postsynaptic currents and their short-term plasticity were normal. These results indicate that, in the cerebellar cortex, chronically elevated levels of soluble Aβ1–42 are associated with alterations of the intrinsic excitability of PCs and with alterations of the release of GABA from interneurons and of glutamate from climbing fibers, while the release of glutamate from parallel fibers and all postsynaptic mechanisms are preserved. Thus, soluble Aβ1–42 causes, in PCs, multiple functional alterations, including an impairment of intrinsic membrane properties and synapse-specific deficits, with differential consequences even in different subtypes of glutamatergic synapses

Retrieval induces adaptive forgetting of competing memories via cortical pattern suppression

Remembering a past experience can, surprisingly, cause forgetting. Forgetting arises when other competing traces interfere with retrieval and inhibitory control mechanisms are engaged to suppress the distraction they cause. This form of forgetting is considered to be adaptive because it reduces future interference. The effect of this proposed inhibition process on competing memories has, however, never been observed, as behavioral methods are 'blind' to retrieval dynamics and neuroimaging methods have not isolated retrieval of individual memories. We developed a canonical template tracking method to quantify the activation state of individual target memories and competitors during retrieval. This method revealed that repeatedly retrieving target memories suppressed cortical patterns unique to competitors. Pattern suppression was related to engagement of prefrontal regions that have been implicated in resolving retrieval competition and, critically, predicted later forgetting. Thus, our findings demonstrate a cortical pattern suppression mechanism through which remembering adaptively shapes which aspects of our past remain accessible

Cueing listeners to attend to a target talker progressively improves word report as the duration of the cue-target interval lengthens to 2000 ms

Endogenous attention is typically studied by presenting instructive cues in advance of a target stimulus array. For endogenous visual attention, task performance improves as the duration of the cue-target interval increases up to 800 ms. Less is known about how endogenous auditory attention unfolds over time or the mechanisms by which an instructive cue presented in advance of an auditory array improves performance. The current experiment used five cue-target intervals (0, 250, 500, 1000, and 2000 ms) to compare four hypotheses for how preparatory attention develops over time in a multi-talker listening task. Young adults were cued to attend to a target talker who spoke in a mixture of three talkers. Visual cues indicated the target talker’s spatial location or their gender. Participants directed attention to location and gender simultaneously (‘objects’) at all cue-target intervals. Participants were consistently faster and more accurate at reporting words spoken by the target talker when the cue-target interval was 2000 ms than 0 ms. In addition, the latency of correct responses progressively shortened as the duration of the cue-target interval increased from 0 to 2000 ms. These findings suggest that the mechanisms involved in preparatory auditory attention develop gradually over time, taking at least 2000 ms to reach optimal configuration, yet providing cumulative improvements in speech intelligibility as the duration of the cue-target interval increases from 0 to 2000 ms. These results demonstrate an improvement in performance for cue-target intervals longer than those that have been reported previously in the visual or auditory modalities

Pharyngoesophageal diverticulum: a delayed complication of anterior cervical spine surgery

Pharyngoesophageal diverticulum after anterior cervical spine surgery is a rarely reported but potentially life-threatening complication. A case report of pharyngoesophageal diverticulum 7 years after anterior cervical spine surgery is presented. The patient suffered from dysphagia, odynophagia, recurrent fever, weight loss, and also an impressive bulging in the neck with swallowing. After careful examination and preparation, he underwent revision surgery via an open procedure, had the implants removed, pouch excised, and esophagus reconstructed reinforced by a sternohyoid muscle flap as well as an omohyoid muscle flap. The post-operative period was uneventful, and he experienced a satisfactory recovery. At last follow up, 2.5 years post surgery, the patient remained symptom free. Upon review of the literature, only six such previous reports with seven cases were found. Diagnostic tools, possible mechanism, correlative factors and treatment are discussed. This patient was fortunate that although his symptoms developed long after the initial anterior cervical operation and the pouch grew impressively large almost perforating, he still recovered well. It again proves the necessity of long-term X-ray follow up, and also reminds the surgeons to be alert of the possibility of esophageal injury even when the esophageal symptoms are mild and occur long after the initial operation