Volume 20 - Issue 7

October 2016

Davide Amato, Editor-in-chief

Pushpanathan Muthuirulan, Guest Editor

In This Issue...

  1. Neuroscience Technologies
  2. Linking neuroimaging and neuropathology in a transgenic rat model for sporadic schizophrenia
  3. IBNS Meeting Impressions
  4. 26th Annual IBNS Meeting: Save the Date!
  5. An Introduction
  6. Trending Science
  7. Japanese Basics

Neuroscience Technologies

By Pushpanathan Muthuirulan

The last decade was an incredible time for neuroscience research as a number of technological breakthroughs have been made, sparking a deeper understanding of normal and pathological brain mechanisms. We decided to showcase six of our favorite innovations in neuroscience that are of note to our IBNS readers.

(1)   Stem cell Technology

Stem cells have been an area of mystery and scientific intrigue that afford plasticity to regenerate, repair and modulate nervous system function. Establishment of neural stem cells (NSCs) as a life-long source of neurons and glia is considered as one of the landmark achievement in neuroscience research. New advances in stem cell technology enable discovery of novel therapies based on the knowledge and application of these unique heterogeneous population of cells, which can differentiate into different types of brain cells. In combination with reprogramming technology, human somatic cell-derived neural stem cells and their progeny can be used as a model for neurological diseases with improved accuracy. Further, human pluripotent stem cells offer attractive source for mechanistic, transplantation and drug screening approaches that provides new dimension to translate validated research findings into new regenerative therapies for neurodegenerative diseases. Other emerging features of stem cell research includes identification of transcription factors and morphogens essential for specific phenotype attributes and differentiation of therapeutically relevant neurons from human pluripotent stem cells. Thus, stem cell technology provides exciting platform for translational medicine aiming to develop reparative and regenerative therapeutic approaches for neurodegenerative disorders.

(2) Brain Organoids

Brain organoids is a miniature, organ-like structures that mimic layered organization of the cells in the brain. Brain organoids has uncovered the mysteries of dementia, mental illness and other neurological disorders. Combination of induced pluripotent stem (iPS) cell technology and three-dimensional culture techniques allows reprogramming of brain cells to neurons and generate brain organoids, which facilitate researchers to zoom in on the brain and connect dots from broken genes to malfunctioning cellular pathways to cell growth associated with brain development. Generating brain organoids from the brain cells obtained from patients and healthy individuals would provide neuroscientist a chance to look at brain development in three-dimensional context and test prospective therapies.

(3) Genome editing

The advent of new genome editing method known as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) has been timed perfectly with the modern neuroscience research.  CRISPR can be used to make specific changes to target region in the genome and has become instrumental in investigating disease mechanism in laboratory due to it low cost, greater precision and ease of use. During recent past, researchers have utilized gene sequencers to uncover genes that are essential for brain development and neurological diseases. Unlike other genome editing methods, CRISPR system can be used to make changes in any stretch of DNA that gives us clues to figure out if disruption of target genes can cause of neurological disease. Till date, neuroscientist have created more animal (insect, mouse, mammal) and cell models using CRISPR technology to study the effect of genetic changes on neural development. Thus, CRISPR technology is accelerating the pace of neuroscience research and enable target genetic interrogation in any organism and cell type, which opened the door for development of new model systems for studying neurological disorders.

(4) Optogenetics

Optogenetic approaches have revolutionized the field of neuroscience and allowed characterization of individual neurons or whole neuronal network through activation or silencing specific regions in the brain. The optogenetic tools hold promise with the potential for modulating activity of brain circuits involved in neurological disorders. During recent years, neuroscientists have used this approach to characterize neural circuits associated with brain disorders using light sensitive proteins such as halorhodopsin and channelrhodopsin. An effort is currently being devoted to refine optogenetic techniques employing viruses to effectively deliver genes that encodes rhodopsin. Thus, optogenetic approaches offers great opportunities for basic neuroscience research and holds promise for rendering neurological therapeutic strategies in future.

(5) Synaptogenic biosensor

GRASP is a novel biosensor based technique that relies on the use of split GFP fragments (GFP1-10 and GFP11) that become fluorescent when reconstituted with each other. In GRASP, each fragment is fused to the extracellular domains for pre- and postsynaptic transmembrane proteins. When pre and postsynaptic neurons come into close proximity to form a synapse, split GFP reconstitutes its fluorescence’s and marks the location of synapse. Further improvement in this method uses split FPs of different colors to simultaneously label different types of synapses. This method allows effective visualization of synapses in living neurons and therefore can be used in mapping brain connectomes.

(6) Transcriptome sequencing

Next-generation sequencing (NGS) technology is rapidly changing its ability to probe molecular basis of neuronal function. NGS can be used to effectively define complete molecular signatures of neurons by transcriptome analysis. RNA-seq has greater dynamic range, detects both abundant and less abundant transcripts, superior for gene network construction and extract genotype information. Further, single-nuclei RNA sequencing of activated neurons enables investigation of gene expression that can offer insight into molecular dynamics associated with different neuronal response. Thus, RNA-seq embraces the complexity of brain transcriptome and provides insight into brain-behavior-disease relationship.

A decade ago, that would have not been technologically possible. But in the recent past, neuroscience has been transformed by remarkable technologies that opened up doors to investigate brain function and develop new therapeutic approaches for neurological disorders.

Linking neuroimaging and neuropathology in a transgenic rat model for sporadic schizophrenia

by Anthony C. Vernon

King’s College London, Institute of Psychiatry, Psychology and Neuroscience, Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience Institute and Psychosis Clinical Academic Group, London UK.

Antipsychotic drugs (APD) targeting dopamine D2 receptors are the mainstay for pharmacological treatment of schizophrenia. Since the introduction of these medications from more than 50 years ago and despite decades of extensive research effort, only little progress has been made in advancing novel non-dopaminergic therapeutics. This reflects our emerging understanding of the complex, multi-factorial nature of schizophrenia pathophysiology driven by advancement in psychiatric genetics, post-mortem brain tissue studies, and neuroimaging, particularly in prodromal individuals transitioning into psychosis. Combination of these approaches are beginning point to draw a picture that schizophrenia is a complex syndrome, with likely multiple aetiologies and potentially distinct neurobiological phenotypes having profound implications for clinical therapeutics. These insights will undoubtedly unlock novel drug treatments for schizophrenia, beyond dopamine and D2 receptor.

Given the urgent medical need, another view suggests that deeper understanding of mechanism of action of APD on the brain and body by investigating cellular, molecular and physiological effects in relevant model systems are paramount importance to expedite the quest for novel and improved medications. This systematic approach is likely to provide in-depth knowledge on mechanisms underlying the beneficial and harmful effects APD. Towards highlighting this view, Dr. Davide Amato (Friedrich-Alexander University, Erlangen, Germany) and me in close collaboration with Dr. Margret Hahn (University of Toronto) and Dr. Clare Beasley (University of British Columbia) organized a symposium on “Neuroadaptations to antipsychotic drugs” at the IBNS meeting in Victoria, Vancouver Island, Canada during 2014. Building on this platform, recently we had presented an updated synthesis of our innovative ideas and latest finding from our complementary lines of research in follow up symposium at 2016 IBNS meeting in Budapest joined with Dr Franceso Papaleo (Italian Institute of Technology, Torino). Compiling all these work together, recently we have published an article in Neuroscience and Biobehavioral Reviews (Amato et al., 2016).

Based on these two exciting symposia, we have reviewed recent advances in our understanding of neuroadaptations to antipsychotics focusing on (1) treatment efficacy (Dr. Davide Amato), (2) impact on brain volume (Dr. Anthony Vernon), (3) evidence from human post-mortem studies attempt to dissect neuropathological effects of antipsychotic drugs from organic schizophrenia neurobiology (Dr. Clare Beasley) and (4) cardio-metabolic side effects (Dr. Margret Hahn). A parsimonious synthesis of these parallel lines of research suggested the following conclusions. First, in terms of antipsychotic efficacy, the serotonin output pattern of APD may offer an improved means of classification, compared to the 5-HT2A/D2 ratio for defining the mechanism of action of antipsychotics, particularly for newer SGA compounds and likely their clinical efficacy. In context, we present the first suggestion that clinical out- comes should be examined based on their relationship with the serotonin and other neurotransmitter output driven by different APD. This efficacy biomarker as defined here may be valuable for investigating the mechanisms of treatment failure. Secondly, based compelling evidence from both clinical and pre-clinical MRI studies, the dose and duration of APD treatment is associated with alterations in brain volume. Nevertheless, important questions on mechanism driving this effect and differential effects of different antipsychotics remain largely unknown. More importantly, accepting these changes do occur, the ultimate clinical consequences of antipsychotic-induced changes in brain volume remain unclear. While post-mortem brain studies in schizophrenia implicate alterations in synapses and glial cells, the potential impact, if any, of APDs on these findings remains to be determined, although evidence suggest that some features, particularly cortical pre-synaptic changes appear to be organic to the disease progression. Finally, it has been long accepted that antipsychotics induce detrimental metabolic alterations, particularly SGA. Yet surprisingly little is still known about the mechanisms underlying these effects, how to obviate them and how they impact on brain structural and behavioral observations in patients.

Ultimately, we propose that gaining a in depth knowledge on the effects of long-term APD treatment on the brain and body at the cellular and molecular level, may ultimately inform the clinical use of these drugs and, moreover, the development of new antipsychotic agents.

Please cite this article in press as:

Amato, D., et al., Neuroadaptations to antipsychotic drugs: Insights from pre-clinical and human post-mortem studies. Neurosci. Biobehav. Rev. (2016), http://dx.doi.org/10.1016/j.neubiorev.2016.10.004

IBNS Meeting Impressions

Henry Szechtman
Professor of Psychiatry and Behavioural Neurosciences
McMaster University

"...I was pleased to see many young faculty members and students.  I take this as a sign of continued vitality and interest in the science at the core of IBNS, namely, behavioral neuroscience.  At the same time, I am also very pleased to see my colleagues returning to the meeting...The venue was terrific as always and the meeting run smoothly from the perspective of a participant.  Many thanks to Marianne for facilitating and arranging a Skype session for one of the participants in our symposium who could not come at the last moment; the session worked out very well. I always look forward to the IBNS meeting because its intimate format provides a venue for renewals as well as learning and this year was no exception."

26th Annual IBNS Meeting: Save the Date!

Join the International Behavioral Neuroscience Society (IBNS) for the 26th Annual Meeting on June 26-30, 2017. Hear from best in our fields of study, establish network with scientists and researchers from all over the world, show case your work and visit Hiroshima, Japan, a vibrant city with a rich culture.


An Introduction

We would like to introduce our local organizing committee (LOC) members for IBNS2017 in Hiroshima on June 26-30, 2017.

This month, we introduce you to Yoichi Ueta (Chair of LOC, Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan) (Photo: Victoria, Canada, IBNS2015) is IBNS member since 1993, Fellow since 2006 and Council member (2004-2007 and 2012-2015). Main research interest is neuroendocrine responses to various stress conditions.


Trending Science

In this column, we will share the latest research, interesting scientific articles and news you can use.

Transplanted embryonic neurons integrate into adult neocortical circuits

Falkner et al. (2016), Nature

In this article, authors have found that grafted embryonic neurons can integrate into neocortical circuits with greater specificity in the adult brain, which open up new avenues for transplanting new neurons into brain that can compensate neuronal loss caused by injury or diseases. Read more here...

Japanese Basics

Thank you

Doumo arigatou
Thanks a lot

Arigatou gozaimasu
Polite form of thank you (Arigatou.)

Daumo arigatou gozaimasu
Thank you very much


IBNS Central Office | 1123 Comanche Path, Bandera, TX 78003 | [email protected]


Join the International Behavioral Neuroscience Society (IBNS) for the 26th Annual Meeting on June 26-30, 2017. Hear from best in our fields of study, establish network with scientists and researchers from all over the world, show case your work and visit Hiroshima, Japan, a vibrant city with a rich culture.