To understand the brain – the 2016 annual meeting of society for neurosciences: a conference report

Abstract

In terms of treatment, oxytocin was found to promote maternal bonding and reduce social impairments in animal models of autism, suggesting a new therapeutic strategy (Alaerts et al., 2016; Harony-Nicolas, 2016). Transplanting embryonic stem cells into the adult brain in a rat model of autism improved symptoms (Donegan et al., 2016). [...]a new experimental drug, GENZ-667161, which inhibits the production of glucocerebrosides, showed reduced level of misfolded α-synuclein (Sardi et al., 2016).

Overview: Over 30,000 neuroscientists participated in the 46th annual meeting of the Society for Neurosciences (SfN 2016), which was held in San Diego, California from November 12th to 16th. More than 15,000 research projects were presented or discussed in the world's largest conference in biomedical sciences. The scope of SfN 2016 broadly covered numerous fields of brain researches, such as neural development, neural excitability and synapses, neurodegenerative disorders, sensory and motor systems, integrative physiology and behavior, motivation and emoting, cognition, etc. Several highlights were summarized below.

Autism: As a disease affecting over 20 million people worldwide, autism has drawn increasing attentions from global neuroscientists in the past few years. New findings presented in the SfN 2016 helped uncover the potential environmental and neurological causes, as well as new treatment strategies for autism. Exposure to pesticides in a rat model was found to produce autism-like symptoms, suggesting a possible environmental link between pesticides and the disease (Berg et al., 2016). The amygdala in autistic patients overproduced dendritic spine and synaptic connections (Weir et al., 2016). Such findings may be associated with the high rate of anxiety in people with autism. Studies also explored a possible role of actin in autism (Kim, 2016; Pyronneau et al., 2016; Yan, 2016). In terms of treatment, oxytocin was found to promote maternal bonding and reduce social impairments in animal models of autism, suggesting a new therapeutic strategy (Alaerts et al., 2016; Harony-Nicolas, 2016). Last but not the least, stem cells have become a useful tool in the autistic research. Serotoninergic neurons were successfully obtained from induced pluripotent stem cells (Feng, 2016; Zhang, 2016). Transplanting embryonic stem cells into the adult brain in a rat model of autism improved symptoms (Donegan et al., 2016). All these findings may allow scientists to better understand the disease and develop better treatment approaches for the major symptoms.

Alzheimer's disease (AD): As one of the two most common neurodegenerative disorders, AD is affecting approximately 48 million people worldwide. In SfN 2016, focuses have been put on early detection, genetic analysis and neural protection of this disease. New findings in AD suggested changes in circadian rhythms may play a role in early detection of the disease. Disruption of sleep-awake cycles was found to present even before symptoms of AD occurred (Phan et al., 2016). Another study showed individuals carrying APOE4, a variant of the apolipoprotein E gene, were more likely to develop AD, because this gene variant was thought to contribute to the accumulation of brain plaques in the early stages of AD (Liu et al., 2016). In addition, a surprising finding revealed that plaques and tangles, which are thought to be characteristic of AD, could also be found in the brain of cognitively healthy elderly people (Rezvanian et al., 2016). This suggested some kind of protective mechanism against dementia was present in their brains.

Parkinson's disease (PD): PD is another common neurodegenerative disorder, presenting in over 50 million people globally. Several findings regarding the mechanisms and new treatment options of PD have drawn attentions of neuroscientists in SfN 2016. A study in rats showed misfolded α-synuclein, the hallmark of PD, built up in the stomach and intestines before being transported to the brain. It lends support to the hypothesis that PD may originate from peripheral organs (Challis et al., 2016). This protein may also spread within the brain with the help of astrocyte (Rostami et al., 2016). Implantation of dopamine-producing fetal cells showed some success in PD patients without immunosuppression (Freed et al., 2016), making neuronal transplantation possible as a therapeutic approach for PD. However, challenges must be solved before clinical application to a wider extent, such as the massive death of transplanted neurons as well as the difficulty of obtaining enough fetal tissues. Finally, a new experimental drug, GENZ-667161, which inhibits the production of glucocerebrosides, showed reduced level of misfolded α-synuclein (Sardi et al., 2016). This provided a new treatment strategy for PD patients with mutated GBA gene.

Peripheral nerve injury and electrical stimulation: Regeneration of injured peripheral nerve and the subsequent functional recovery may be promoted by application of electrical stimulation and/or neurotrophic factors to the injured site. However, the specificity of muscle reinnervation by a motor nerve was not well understood. In a canine model, researchers found electrical stimulation to the denervated laryngeal abductor muscle at a low frequency promoted the appropriate reinnervation by the intrinsic inspiratory motoneurons (Li et al., 2016), suggesting a possible clinical application of electrical stimulation to prevent synkinesis. In a rat model, however, retrograde labeling and spatial analysis did not show preferential reinnervation of the soleus muscle by electrical stimulation (Willand et al., 2016). Whether electrical stimulation promotes selective reinnervation remains unclear.

Innovation in neuroscience technologies: Advances in technologies presented in SfN 2016 were extraordinary. A new non-invasive technique, named temporal interference stimulation, was developed to deliver targeted deep brain stimulation precisely without any implantation. This technique opens a door for non-invasive treatment to alleviate the tremors and movement issues associated with PD (Grossman et al., 2016). Likewise, a gene called electromagnetic-perceptive gene (EPG) was identified from a type of fish with sensation of the magnetic field. When the gene was expressed in neurons, magnetic stimulation increased their calcium influx. In a rat model with EPG expression in motor cortex, magnetic stimulation was able to control motor output specifically corresponding to the EPG-expressing motoneurons (Banerjee et al., 2016). This finding makes non-invasive neuromodulation a promising approach in neuroscience research, it may also be developed as an advancement of deep brain stimulation for treatment of PD. Another group of researchers developed a new technique called Multiplexed Analysis of Projections by sequencing (MAPseq) to efficiently map out the connections between individual neurons and their targets. They used a virus to label individual cortical neurons with unique RNA barcodes, the RNA barcodes attaching to a protein was transported to the axon terminal. By counting the amount of each RNA barcode in the brain sections, they were able to find out the whole projection map of the brain in a single experiment (Huang et al., 2016). Last but not the least, a brain-computer interface (BCI) has been applied in treatment of advanced amyotrophic lateral sclerosis. The BCI was able to translate the patient's neuronal activities into her thought. Minor activity (controlling a mouse) could be fulfilled in this patient (Pels et al., 2016). This case represents a great example of clinical application of BCI in treating advanced neurodegenerative diseases.

Common fund opportunities: The NIH Common Fund (NFC) was established to support cross-cutting, trans-NIH programs that require participation by at least two NIH Institutes or Centers. Currently there are 30 cross-cutting programs under the support by NFC, including 4D nucleome, stimulating peripheral activity to relieve conditions (SPARC), metabolomics, extracellular RNA communication, regenerative medicine program (RMP), etc. The budget for fiscal year 2017 is 209 million. This is a good source of funding opportunity for PIs whose research requires multidisciplinary collaboration. For example, a research project on stem-cell based therapy to treat age-related macular degeneration has got funded from RMP (Lowenthal et al., 2012).