Pub Date : 2019-01-18eCollection Date: 2019-01-01DOI: 10.1177/2398212818817932
Arjun Ramakrishnan, Benjamin Y Hayden, Michael L Platt
To maximise long-term reward rates, foragers deciding when to leave a patch must compute a decision variable that reflects both the immediately available reward and the time costs associated with travelling to the next patch. Identifying the mechanisms that mediate this computation is central to understanding how brains implement foraging decisions. We previously showed that firing rates of dorsal anterior cingulate sulcus neurons incorporate both variables. This result does not provide information about whether integration of information reflected in dorsal anterior cingulate sulcus spiking activity arises locally or whether it is inherited from upstream structures. Here, we examined local field potentials gathered simultaneously with our earlier recordings. In the majority of recording sites, local field potential spectral bands - specifically theta, beta, and gamma frequency ranges - encoded immediately available rewards but not time costs. The disjunction between information contained in spiking and local field potentials can constrain models of foraging-related processing. In particular, given the proposed link between local field potentials and inputs to a brain area, it raises the possibility that local processing within dorsal anterior cingulate sulcus serves to more fully bind immediate reward and time costs into a single decision variable.
{"title":"Local field potentials in dorsal anterior cingulate sulcus reflect rewards but not travel time costs during foraging.","authors":"Arjun Ramakrishnan, Benjamin Y Hayden, Michael L Platt","doi":"10.1177/2398212818817932","DOIUrl":"10.1177/2398212818817932","url":null,"abstract":"<p><p>To maximise long-term reward rates, foragers deciding when to leave a patch must compute a decision variable that reflects both the immediately available reward and the time costs associated with travelling to the next patch. Identifying the mechanisms that mediate this computation is central to understanding how brains implement foraging decisions. We previously showed that firing rates of dorsal anterior cingulate sulcus neurons incorporate both variables. This result does not provide information about whether integration of information reflected in dorsal anterior cingulate sulcus spiking activity arises locally or whether it is inherited from upstream structures. Here, we examined local field potentials gathered simultaneously with our earlier recordings. In the majority of recording sites, local field potential spectral bands - specifically theta, beta, and gamma frequency ranges - encoded immediately available rewards but not time costs. The disjunction between information contained in spiking and local field potentials can constrain models of foraging-related processing. In particular, given the proposed link between local field potentials and inputs to a brain area, it raises the possibility that local processing within dorsal anterior cingulate sulcus serves to more fully bind immediate reward and time costs into a single decision variable.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":" ","pages":"2398212818817932"},"PeriodicalIF":0.0,"publicationDate":"2019-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212818817932","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37733053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-01DOI: 10.1177/2398212819883088
G. Barker, O. Evuarherhe, E. Warburton
Remembering the sequence, in which stimuli are encountered or events have occurred, is a key process in episodic memory and can also facilitate recognition memory. Rodents, when presented with a sequence of objects, will explore the object encountered first; yet, whether this behaviour is because the rodents spontaneously encode the order of stimuli presentation or because of relative familiarity or temporal decay is unknown. Here, we tested sequence memory in rats using a series of spontaneous preference tasks. Experiment 1 demonstrated that when rats are presented with a sequence of four objects, with an inter-sample interval of 5 min or 1 h, they preferentially explored the object presented earlier in the list irrespective of the inter-sample interval. We then demonstrated that such memory for order was not affected by increasing or decreasing the inter-sample interval between the middle objects (Experiment 2). Finally, we showed that memory for order is not a function of absolute object familiarity, as animals showed clear discrimination between the objects presented in the sample phases and a novel object, independent of the sample objects’ position in the sequence (Experiment 3). These results show that animals are able to encode the order of objects presented in a sequence, and as such temporal order memory is not achieved using the process of relative or absolute familiarity or temporal decay.
{"title":"Remembering the order of serially presented objects: A matter of time?","authors":"G. Barker, O. Evuarherhe, E. Warburton","doi":"10.1177/2398212819883088","DOIUrl":"https://doi.org/10.1177/2398212819883088","url":null,"abstract":"Remembering the sequence, in which stimuli are encountered or events have occurred, is a key process in episodic memory and can also facilitate recognition memory. Rodents, when presented with a sequence of objects, will explore the object encountered first; yet, whether this behaviour is because the rodents spontaneously encode the order of stimuli presentation or because of relative familiarity or temporal decay is unknown. Here, we tested sequence memory in rats using a series of spontaneous preference tasks. Experiment 1 demonstrated that when rats are presented with a sequence of four objects, with an inter-sample interval of 5 min or 1 h, they preferentially explored the object presented earlier in the list irrespective of the inter-sample interval. We then demonstrated that such memory for order was not affected by increasing or decreasing the inter-sample interval between the middle objects (Experiment 2). Finally, we showed that memory for order is not a function of absolute object familiarity, as animals showed clear discrimination between the objects presented in the sample phases and a novel object, independent of the sample objects’ position in the sequence (Experiment 3). These results show that animals are able to encode the order of objects presented in a sequence, and as such temporal order memory is not achieved using the process of relative or absolute familiarity or temporal decay.","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212819883088","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48078685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-01DOI: 10.1177/2398212819883086
Tobias C. Wood, Michelle E. Edye, M. Harte, J. Neill, E. Prinssen, A. Vernon
Maternal immune activation is consistently associated with elevated risk for multiple psychiatric disorders in the affected offspring. Related to this, an important goal of our work is to explore the impact of maternal immune activation effects across the lifespan. In this context, we recently reported the effects of polyriboinosinic-polyribocytidylic acid–induced maternal immune activation at gestational day 15, immediately prior to birth, at gestational day 21 and again at post-natal day 21, providing a systematic assessment of plasma interleukin 6, body temperature and weight alterations in pregnant rats and preliminary evidence for gross morphological changes and microglial neuropathology in both male and female offsprings at these time points. Here, we sought to complement and extend these data by characterising in more detail the mesoscale impact of gestational polyriboinosinic-polyribocytidylic acid exposure at gestational day 15 on the neuroanatomy of the juvenile (post-natal day 21) rat brain using high-resolution, ex vivo anatomical magnetic resonance imaging in combination with atlas-based segmentation. Our preliminary data suggest subtle neuroanatomical effects of gestational polyriboinosinic-polyribocytidylic acid exposure (n = 10) relative to saline controls (n = 10) at this time-point. Specifically, we found an increase in the relative volume of the diagonal domain in polyriboinosinic-polyribocytidylic acid offspring (p < 0.01 uncorrected), which just failed to pass stringent multiple comparisons correction (actual q = 0.07). No statistically significant microstructural alterations were detectable using diffusion tensor imaging. Further studies are required to map the proximal effects of maternal immune activation on the developing rodent brain from foetal to early post-natal life and confirm our findings herein.
{"title":"Mapping the impact of exposure to maternal immune activation on juvenile Wistar rat brain macro- and microstructure during early post-natal development","authors":"Tobias C. Wood, Michelle E. Edye, M. Harte, J. Neill, E. Prinssen, A. Vernon","doi":"10.1177/2398212819883086","DOIUrl":"https://doi.org/10.1177/2398212819883086","url":null,"abstract":"Maternal immune activation is consistently associated with elevated risk for multiple psychiatric disorders in the affected offspring. Related to this, an important goal of our work is to explore the impact of maternal immune activation effects across the lifespan. In this context, we recently reported the effects of polyriboinosinic-polyribocytidylic acid–induced maternal immune activation at gestational day 15, immediately prior to birth, at gestational day 21 and again at post-natal day 21, providing a systematic assessment of plasma interleukin 6, body temperature and weight alterations in pregnant rats and preliminary evidence for gross morphological changes and microglial neuropathology in both male and female offsprings at these time points. Here, we sought to complement and extend these data by characterising in more detail the mesoscale impact of gestational polyriboinosinic-polyribocytidylic acid exposure at gestational day 15 on the neuroanatomy of the juvenile (post-natal day 21) rat brain using high-resolution, ex vivo anatomical magnetic resonance imaging in combination with atlas-based segmentation. Our preliminary data suggest subtle neuroanatomical effects of gestational polyriboinosinic-polyribocytidylic acid exposure (n = 10) relative to saline controls (n = 10) at this time-point. Specifically, we found an increase in the relative volume of the diagonal domain in polyriboinosinic-polyribocytidylic acid offspring (p < 0.01 uncorrected), which just failed to pass stringent multiple comparisons correction (actual q = 0.07). No statistically significant microstructural alterations were detectable using diffusion tensor imaging. Further studies are required to map the proximal effects of maternal immune activation on the developing rodent brain from foetal to early post-natal life and confirm our findings herein.","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212819883086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48519654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-12eCollection Date: 2018-01-01DOI: 10.1177/2398212818816017
Laurie Pycroft, John Stein, Tipu Aziz
Deep brain stimulation has already revolutionised the clinical management of treatment-resistant movement disorders and offers novel treatment options for an increasing range of neurological and psychiatric illnesses. In this article, we briefly review the history of deep brain stimulation, particularly focusing on the last 50 years, which have seen rapid development in the safety and efficacy of deep brain stimulation. We then discuss the current state of the art in deep brain stimulation, focusing on emerging indications and recent technological advances that have improved the field. Finally, we consider the future developments in technology, technique, and research that will impact deep brain stimulation; particularly focusing on closed-loop stimulation techniques and emerging techniques such as optogenetics, cybersecurity risk, implantation timing, and impediments to undertaking high-quality research.
{"title":"Deep brain stimulation: An overview of history, methods, and future developments.","authors":"Laurie Pycroft, John Stein, Tipu Aziz","doi":"10.1177/2398212818816017","DOIUrl":"https://doi.org/10.1177/2398212818816017","url":null,"abstract":"<p><p>Deep brain stimulation has already revolutionised the clinical management of treatment-resistant movement disorders and offers novel treatment options for an increasing range of neurological and psychiatric illnesses. In this article, we briefly review the history of deep brain stimulation, particularly focusing on the last 50 years, which have seen rapid development in the safety and efficacy of deep brain stimulation. We then discuss the current state of the art in deep brain stimulation, focusing on emerging indications and recent technological advances that have improved the field. Finally, we consider the future developments in technology, technique, and research that will impact deep brain stimulation; particularly focusing on closed-loop stimulation techniques and emerging techniques such as optogenetics, cybersecurity risk, implantation timing, and impediments to undertaking high-quality research.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"2 ","pages":"2398212818816017"},"PeriodicalIF":0.0,"publicationDate":"2018-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212818816017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37733222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-12eCollection Date: 2018-01-01DOI: 10.1177/2398212818817499
Kevin Warwick
This article contains a directed overview of the field of neuroengineering and neuroprosthetics. The aim of the article is, however, not to go over introductory material covered elsewhere, but rather to look ahead at exciting areas for likely future development. The BrainGate implant is focussed on in terms of its use as an interface between the Internet and the human nervous system. Sensory prosthetics of different types and deep brain stimulation are considered. Different possibilities with deep brain stimulation are also discussed.
{"title":"Neuroengineering and neuroprosthetics.","authors":"Kevin Warwick","doi":"10.1177/2398212818817499","DOIUrl":"https://doi.org/10.1177/2398212818817499","url":null,"abstract":"<p><p>This article contains a directed overview of the field of neuroengineering and neuroprosthetics. The aim of the article is, however, not to go over introductory material covered elsewhere, but rather to look ahead at exciting areas for likely future development. The BrainGate implant is focussed on in terms of its use as an interface between the Internet and the human nervous system. Sensory prosthetics of different types and deep brain stimulation are considered. Different possibilities with deep brain stimulation are also discussed.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"2 ","pages":"2398212818817499"},"PeriodicalIF":0.0,"publicationDate":"2018-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212818817499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37733606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-10eCollection Date: 2018-01-01DOI: 10.1177/2398212818817497
Maria Pia Giannoccaro, Sarah J Crisp, Angela Vincent
Antibody-mediated central nervous system diseases are a relatively new area of clinical neuroscience with growing impact. Their recognition has challenged the dogma of the blood-brain barrier preventing antibody access into the central nervous system. The antibodies discovered so far are mainly against neurotransmitter receptors (e.g. N-methyl-d-aspartate and glycine receptors) and ion channel-associated proteins (leucine-rich glioma inactivated protein 1 and contactin-associated protein 2) and are expressed on the surface of neuronal synapses and elsewhere. The disorders are reversible with immunotherapies that reduce antibody levels. Although rare, the identification of these disorders in clinical practice has made central nervous system autoimmune diseases a consideration in the differential diagnoses of many clinical presentations. There is still much to learn about the aetiology of the diseases and the mechanisms by which the antibodies act, the neuronal and glial changes that follow antibody-attack, and the compensatory changes that may be required to ensure good recovery.
{"title":"Antibody-mediated central nervous system diseases.","authors":"Maria Pia Giannoccaro, Sarah J Crisp, Angela Vincent","doi":"10.1177/2398212818817497","DOIUrl":"https://doi.org/10.1177/2398212818817497","url":null,"abstract":"<p><p>Antibody-mediated central nervous system diseases are a relatively new area of clinical neuroscience with growing impact. Their recognition has challenged the dogma of the blood-brain barrier preventing antibody access into the central nervous system. The antibodies discovered so far are mainly against neurotransmitter receptors (e.g. <i>N</i>-methyl-d-aspartate and glycine receptors) and ion channel-associated proteins (leucine-rich glioma inactivated protein 1 and contactin-associated protein 2) and are expressed on the surface of neuronal synapses and elsewhere. The disorders are reversible with immunotherapies that reduce antibody levels. Although rare, the identification of these disorders in clinical practice has made central nervous system autoimmune diseases a consideration in the differential diagnoses of many clinical presentations. There is still much to learn about the aetiology of the diseases and the mechanisms by which the antibodies act, the neuronal and glial changes that follow antibody-attack, and the compensatory changes that may be required to ensure good recovery.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"2 ","pages":"2398212818817497"},"PeriodicalIF":0.0,"publicationDate":"2018-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212818817497","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37733224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-07eCollection Date: 2018-01-01DOI: 10.1177/2398212818818068
Lindy Holden-Dye, Robert J Walker
The fundamental processes of neural communication have been largely conserved through evolution. Throughout the last century, researchers have taken advantage of this, and the experimental tractability of invertebrate animals, to advance understanding of the nervous system that translates to mammalian brain. This started with the inspired analysis of the ionic basis of neuronal excitability and neurotransmission using squid during the 1940s and 1950s and has progressed to detailed insight into the molecular architecture of the synapse facilitated by the genetic tractability of the nematode Caenorhabditis elegans and the fruit fly Drosophila melanogaster. Throughout this time, invertebrate preparations have provided a means to link neural mechanisms to behavioural plasticity and thus key insight into fundamental aspects of control systems, learning, and memory. This article captures key highlights that exemplify the historical and continuing invertebrate contribution to neuroscience.
{"title":"Invertebrate models of behavioural plasticity and human disease.","authors":"Lindy Holden-Dye, Robert J Walker","doi":"10.1177/2398212818818068","DOIUrl":"https://doi.org/10.1177/2398212818818068","url":null,"abstract":"<p><p>The fundamental processes of neural communication have been largely conserved through evolution. Throughout the last century, researchers have taken advantage of this, and the experimental tractability of invertebrate animals, to advance understanding of the nervous system that translates to mammalian brain. This started with the inspired analysis of the ionic basis of neuronal excitability and neurotransmission using squid during the 1940s and 1950s and has progressed to detailed insight into the molecular architecture of the synapse facilitated by the genetic tractability of the nematode <i>Caenorhabditis elegans</i> and the fruit fly <i>Drosophila melanogaster</i>. Throughout this time, invertebrate preparations have provided a means to link neural mechanisms to behavioural plasticity and thus key insight into fundamental aspects of control systems, learning, and memory. This article captures key highlights that exemplify the historical and continuing invertebrate contribution to neuroscience.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"2 ","pages":"2398212818818068"},"PeriodicalIF":0.0,"publicationDate":"2018-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212818818068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37733604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-06eCollection Date: 2018-01-01DOI: 10.1177/2398212818817494
Geoffrey Burnstock
Adenosine 5'-triphosphate acts as an extracellular signalling molecule (purinergic signalling), as well as an intracellular energy source. Adenosine 5'-triphosphate receptors have been cloned and characterised. P1 receptors are selective for adenosine, a breakdown product of adenosine 5'-triphosphate after degradation by ectonucleotidases. Four subtypes are recognised, A1, A2A, A2B and A3 receptors. P2 receptors are activated by purine and by pyrimidine nucleotides. P2X receptors are ligand-gated ion channel receptors (seven subunits (P2X1-7)), which form trimers as both homomultimers and heteromultimers. P2Y receptors are G protein-coupled receptors (eight subtypes (P2Y1/2/4/6/11/12/13/14)). There is both purinergic short-term signalling and long-term (trophic) signalling. The cloning of P2X-like receptors in primitive invertebrates suggests that adenosine 5'-triphosphate is an early evolutionary extracellular signalling molecule. Selective purinoceptor agonists and antagonists with therapeutic potential have been developed for a wide range of diseases, including thrombosis and stroke, dry eye, atherosclerosis, kidney failure, osteoporosis, bladder incontinence, colitis, neurodegenerative diseases and cancer.
{"title":"Purine and purinergic receptors.","authors":"Geoffrey Burnstock","doi":"10.1177/2398212818817494","DOIUrl":"https://doi.org/10.1177/2398212818817494","url":null,"abstract":"<p><p>Adenosine 5'-triphosphate acts as an extracellular signalling molecule (purinergic signalling), as well as an intracellular energy source. Adenosine 5'-triphosphate receptors have been cloned and characterised. P1 receptors are selective for adenosine, a breakdown product of adenosine 5'-triphosphate after degradation by ectonucleotidases. Four subtypes are recognised, A<sub>1</sub>, A<sub>2A</sub>, A<sub>2B</sub> and A<sub>3</sub> receptors. P2 receptors are activated by purine and by pyrimidine nucleotides. P2X receptors are ligand-gated ion channel receptors (seven subunits (P2X1-7)), which form trimers as both homomultimers and heteromultimers. P2Y receptors are G protein-coupled receptors (eight subtypes (P2Y<sub>1/2/4/6/11/12/13/14</sub>)). There is both purinergic short-term signalling and long-term (trophic) signalling. The cloning of P2X-like receptors in primitive invertebrates suggests that adenosine 5'-triphosphate is an early evolutionary extracellular signalling molecule. Selective purinoceptor agonists and antagonists with therapeutic potential have been developed for a wide range of diseases, including thrombosis and stroke, dry eye, atherosclerosis, kidney failure, osteoporosis, bladder incontinence, colitis, neurodegenerative diseases and cancer.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"2 ","pages":"2398212818817494"},"PeriodicalIF":0.0,"publicationDate":"2018-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212818817494","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37733605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-05eCollection Date: 2018-01-01DOI: 10.1177/2398212818817498
David Cunningham Owens, Eve C Johnstone
Antipsychotic drugs revolutionised psychiatric practice and provided a range of tools for exploring brain function in health and disease. Their development and introduction were largely empirical but based on long and honourable scientific credentials and remarkable powers of clinical observation. The class shares a common core action of attenuating central dopamine transmission, which underlies the major limitation to their use - high liability to disrupt extrapyramidal function - and also the most durable hypothesis of the basis of psychotic disorders, especially schizophrenia. However, the Dopamine Hypothesis, which has driven drug development for almost half a century, has become a straight-jacket, stifling innovation, resulting in a class of compounds that are largely derivative. Recent efforts only cemented this tendency as no clinical evidence supports the notion that newer compounds, modelled on clozapine, share that drug's unique neurological tolerability and can be considered 'atypical'. Patients and doctors alike must await a more profound understanding of central dopamine homeostasis and novel methods of maintaining it before they can again experience the intoxicating promise antipsychotics once held.
{"title":"The development of antipsychotic drugs.","authors":"David Cunningham Owens, Eve C Johnstone","doi":"10.1177/2398212818817498","DOIUrl":"10.1177/2398212818817498","url":null,"abstract":"<p><p>Antipsychotic drugs revolutionised psychiatric practice and provided a range of tools for exploring brain function in health and disease. Their development and introduction were largely empirical but based on long and honourable scientific credentials and remarkable powers of clinical observation. The class shares a common core action of attenuating central dopamine transmission, which underlies the major limitation to their use - high liability to disrupt extrapyramidal function - and also the most durable hypothesis of the basis of psychotic disorders, especially schizophrenia. However, the Dopamine Hypothesis, which has driven drug development for almost half a century, has become a straight-jacket, stifling innovation, resulting in a class of compounds that are largely derivative. Recent efforts only cemented this tendency as no clinical evidence supports the notion that newer compounds, modelled on clozapine, share that drug's unique neurological tolerability and can be considered 'atypical'. Patients and doctors alike must await a more profound understanding of central dopamine homeostasis and novel methods of maintaining it before they can again experience the intoxicating promise antipsychotics once held.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"2 ","pages":"2398212818817498"},"PeriodicalIF":0.0,"publicationDate":"2018-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2d/6d/10.1177_2398212818817498.PMC7058266.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37733225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2018-12-05eCollection Date: 2018-01-01DOI: 10.1177/2398212818818071
Kirsty Goncalves, Stefan Przyborski
The use of stem cells in biomedical research is an extremely active area of science. This is because they provide tools that can be used both in vivo and vitro to either replace cells lost in degenerative processes, or to model such diseases to elucidate their underlying mechanisms. This review aims to discuss the use of stem cells in terms of providing regeneration within the nervous system, which is particularly important as neurons of the central nervous system lack the ability to inherently regenerate and repair lost connections. As populations are ageing, incidence of neurodegenerative diseases are increasing, highlighting the need to better understand the regenerative capacity and many uses of stem cells in this field.
{"title":"The utility of stem cells for neural regeneration.","authors":"Kirsty Goncalves, Stefan Przyborski","doi":"10.1177/2398212818818071","DOIUrl":"https://doi.org/10.1177/2398212818818071","url":null,"abstract":"<p><p>The use of stem cells in biomedical research is an extremely active area of science. This is because they provide tools that can be used both in vivo and vitro to either replace cells lost in degenerative processes, or to model such diseases to elucidate their underlying mechanisms. This review aims to discuss the use of stem cells in terms of providing regeneration within the nervous system, which is particularly important as neurons of the central nervous system lack the ability to inherently regenerate and repair lost connections. As populations are ageing, incidence of neurodegenerative diseases are increasing, highlighting the need to better understand the regenerative capacity and many uses of stem cells in this field.</p>","PeriodicalId":72444,"journal":{"name":"Brain and neuroscience advances","volume":"2 ","pages":"2398212818818071"},"PeriodicalIF":0.0,"publicationDate":"2018-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2398212818818071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37733608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}