Awareness is essential for differential delay eyeblink conditioning with soft-tone but not loud-tone conditioned stimuli

The role of awareness in differential delay eyeblink conditioning （DEC） remains controversial. Here, we investigated the involvement of awareness in differential DEC with a soft or a loud tone as the conditioned stimulus （CS）. In the experiment, 36 participants were trained in differential DEC with a soft tone （60 dB） or a loud tone （85 dB） as the CS, paired with a corneal air-puff as the unconditioned stimulus （US）. After conditioning, awareness of the relationship between assessed with a 17-item the CS and the US was true/false questionnaire. Interestingly, during differential DEC with a soft-tone CS, a higher proportion of differential conditioned responses （CRs） was evident in participants who were aware than those who were unaware. In contrast, when a loud tone was used as the CS, the proportion of differential CRs of the aware participants did not differ significantly from those who were unaware over any of the blocks of 20 trials. In unaware participants, the percentage of differential CRs with a loud-tone CS was significantly higher than that with a soft-tone CS; however in participants classified as aware, the percentage of differential CRs with a loud-tone CS did not differ significantly from that with a soft-tone CS. The present findings suggest that awareness is critical for differential DEC when the delay task is rendered more difficult.

Cardiac Remote Conditioning and Clinical Relevance:All Together Now!

Acute myocardial infarction （AMI） is the leading cause of death and disability worldwide. Timely reperfusion is the standard of care and results in decreased infarct size, improving patient survival and prognosis. However, 25% of patients proceed to develop heart failure （HF） after myocardial infarction （MI） and 50% of these will die within five years. Since the size of the infarct is the major predictor of the outcome, including the development of HF, therapies to improve myocardial salvage have great potential. Over the past three decades, a number of stimuli have been discovered that activate endogenous cardioprotective pathways. In ischemic preconditioning （IPC） and ischemic postconditioning, ischemia within the heart initiates the protection. Brief reversible episodes of ischemia in vascular beds remote from the heart can also trigger cardioprotection when applied before, during, or immediately after myocardial ischemia-- known as remote ischemic pre-, per-, and post-conditioning, respectively. Although the mechanism of remote ischemic preconditioning （RIPC） has not yet been fully elucidated, many mechanistic components are shared with IPC. The discovery of RIPC led to research into the use of remote non-ischemic stimuli including nerve stimulation （spinal and vagal）, and electroacupuncture （EA）. We discovered and, with others, have elucidated mechanistic aspects of a non- ischemic phenomenon we termed remote preconditioning of trauma （RPCT）. RPCT operates via neural stimulation of skin sensory nerves and has similarities and differences to nerve stimulation and EA conducted at acupoints. We show herein that RPCT can be mimicked using electrical stimulation of the abdominal midline （EA-like treatment） and that this modality of activating cardioprotection is powerful as both a preconditioning and a postconditioning stimulus （when applied at reperfusion）. Investigations of these cardioprotective phenomena have led to a more integrative understanding of mechanisms related to cardioprotection, and in the last five to ten years, it has become clear that the mechanisms are similar, whether induced by ischemic or non-ischemic stimuli. Taking together much of the data in the literature, we propose that all of these cardioprotective ＂conditioning＂ phenomena represent activation from different entry points of a cardiac conditioning network that converges upon specific mediators and effectors of myocardial cell survival, including NF-KB, Stat3/5, protein kinase C, bradykinin, and the mitoKA^P channel. Nervous system pathways may represent a novel mechanism for initiating conditioning of the heart and other organs. IPC and RIPC have proven difficult to translate clinically, as they have associated risks and cannot be used in some patients. Because of this, the use of neural and nociceptive stimuli is emerging as a potential non-ischemic and non-traumatic means to initiate cardiac conditioning. Clinical relevance is underscored by the demonstration of postconditioning with one of these modalities, supporting the conclusion that the development of pharmaceuticals and electroceuticals for this purpose is an area ripe for clinical development.

Establishment of Visual Fear Conditioning in Long-evans Rats

The neural mechanisms underlying visual information transmission and coding are currently attracting the attention of neuroscience and brain-like computing scholars.The subcortical visual pathway is known to affect fear emotion regulation via the amygdala;however an experimental paradigm for visual fear cognition training remains undefined.In this study,Long-Evans(LE)rats were used to develop an experimental training paradigm for visual cognition-associated fear conditioning based on the Pavlovian conditioning reflex.Simple images were shown on a unilateral screen(conditioned stimulus)were combined with electric foot shocks(unconditioned stimulus).We designed training paradigms and set up an estimated index using the rate of successful active escape.The training results were analyzed using a two-way ANOVA,and curve fitting was used to analyze the influence of decision time between the conditioned stimulus(CS)and unconditioned stimulus(US)on choice behavior.While neither the CS nor US had a significant effect on visual fear association training in LE rats,the decision time duration(CS-US)did have an impact on training.The method described here is most effective in establishing visual fear associations in rats when the(CS-UC)=10 s.This study describes a new experimental training paradigm for fear conditioning using visual stimuli and a quantitative evaluation standard according to the training mode of visual stimulation graphics.Moreover,it is an efficient paradigm for future study on visual information-processing mechanisms in the subcortical visual pathway during fear conditioning.