title: General Anaesthetic Modulation of Memory-Related Gene Expression in the Cerebral Cortex

authors: Bell, Laura Maree

subjects: Anaesthetic

abstract: General anaesthetics have been widely used in a clinical setting, having remained one of the most important drugs in medicine for their role in enabling major surgical procedures to be carried out. One of the fundamental outcomes of an anaesthetic is amnesia, as this prevents patient recall of events surrounding surgery. The hippocampal region of the mammalian brain has been investigated for its role in memory formation, however the cerebral cortex also has recognised importance in memory consolidation and storage processes. General anaesthetics cause widespread neurochemical changes in the brain and the disruption to memory consolidation processes is likely to involve alteration to the expression patterns of memory-related genes. The aim of this research was to investigate the cerebrocortical gene expression pattern of five memory-related genes, Arc, Bdnf, CaMKIIα, Gjd2 and Grin1 during exposure to anaesthesia induced by sevoflurane, isoflurane and propofol. Real-time quantitative PCR (qPCR) was used to analyse expression of the individual mRNA transcripts and REST© software was used to carry out statistical analysis of the mRNA expression of each gene of interest. Our research demonstrated that Bdnf was significantly down-regulated by sevoflurane at t=2 hours and t=4 hours and propofol at t=2 hours (p<0.05). Up-regulation of Arc after a four exposure to propofol was also observed but no change in Arc was found at the other time points. There was no change in the expression of CaMKIIα, Gjd2 or Grin1 during sevoflurane- or propofol- induced anaesthesia. We recommend analysis of other Bdnf transcript variants in the mouse brain during anaesthesia, as well as levels of the BDNF protein to further validate these results.

text: General Anaesthetic Modulation of Memory-Related Gene Expression in the Cerebral Cortex General anaesthetics have been widely used in a clinical setting, having remained one of the most important drugs in medicine for their role in enabling major surgical procedures to be carried out. One of the fundamental outcomes of an anaesthetic is amnesia, as this prevents patient recall of events surrounding surgery. The hippocampal region of the mammalian brain has been investigated for its role in memory formation, however the cerebral cortex also has recognised importance in memory consolidation and storage processes. General anaesthetics cause widespread neurochemical changes in the brain and the disruption to memory consolidation processes is likely to involve alteration to the expression patterns of memory-related genes. The aim of this research was to investigate the cerebrocortical gene expression pattern of five memory-related genes, Arc, Bdnf, CaMKIIα, Gjd2 and Grin1 during exposure to anaesthesia induced by sevoflurane, isoflurane and propofol. Real-time quantitative PCR (qPCR) was used to analyse expression of the individual mRNA transcripts and REST© software was used to carry out statistical analysis of the mRNA expression of each gene of interest. Our research demonstrated that Bdnf was significantly down-regulated by sevoflurane at t=2 hours and t=4 hours and propofol at t=2 hours (p<0.05). Up-regulation of Arc after a four exposure to propofol was also observed but no change in Arc was found at the other time points. There was no change in the expression of CaMKIIα, Gjd2 or Grin1 during sevoflurane- or propofol- induced anaesthesia. We recommend analysis of other Bdnf transcript variants in the mouse brain during anaesthesia, as well as levels of the BDNF protein to further validate these results.

year: 2015

title: Peak Shift in Remembering

authors: Hoan, Andros

subjects: memory trace

abstract: If remembering is discriminative behaviour along the dimension of time and if, as Sargisson and White (2001) argued, generalisation around a peak can occur in this behaviour, then the peak shift which has been shown in discrimination along so many other stimulus dimensions, might also occur in remembering. To examine this hypothesis, 6 hens were trained in a delayed matching-to-sample procedure at delays of 2 and 4 s. The probability of reinforcement for correct responses was initially 0.9 at both delays until performance stabilised. A generalisation probe was then carried out by inserting unreinforced trials at delays of 0, 1, 1.5, 2.5, 3, 3.5, 4.5, 5 and 6 s in a session amongst normal training delay trials. The generalisation functions had a slight peak around 2 s. After further training, a second generalisation probe showed a slightly declining function. The probability of reinforcement at the 2 s delay was then dropped to 0.1, so that in the terms of the classical generalisation/peak shift paradigm, 2-s delay trials became S- and 4-s delay trials became S+. A third generalisation probe then was conducted. This resulted in a flat function from 0 s to 3 s, and a large, clear peak in discriminative performance at 4.5 s over all hens. After more of the same differential reinforcement training, a fourth generalisation probe showed a broad curve peaking at 3 s, with minima at 1 s and 6 s and a global maximum at 0 s. Another training condition was then run, with the probability of reinforcement at the 2-s delay dropped to 0, to see if increasing the "aversiveness" of S- would again result in a peak shift. A fifth generalisation probe was then conducted. This showed a sharp decline in discriminability at shorter delays, a dip around 2 s, and a very small area shift beyond 4 s, but no clear peak shift. This was interpreted as being due to overlearning, with the consequences of remembering at S- no longer significantly affecting performance at S+. A final training condition was then run, with S- moved from 2 s to 3 s with zero probability of reinforcement, and for only a short period, to prevent overlearning. It was predicted that this would cause peak shift to re-occur. A sixth generalisation probe was then conducted. This found a further decline in discriminability at shorter delays, a shift in the dip from 2 s to 3 s, and a large, clear peak at 4.5 s. This demonstration of peak shift in a remembering process would not have been predicted by any traditional theory of memory, but strongly supports the conception of remembering as discriminative behaviour along the stimulus dimension of time.

text: Peak Shift in Remembering If remembering is discriminative behaviour along the dimension of time and if, as Sargisson and White (2001) argued, generalisation around a peak can occur in this behaviour, then the peak shift which has been shown in discrimination along so many other stimulus dimensions, might also occur in remembering. To examine this hypothesis, 6 hens were trained in a delayed matching-to-sample procedure at delays of 2 and 4 s. The probability of reinforcement for correct responses was initially 0.9 at both delays until performance stabilised. A generalisation probe was then carried out by inserting unreinforced trials at delays of 0, 1, 1.5, 2.5, 3, 3.5, 4.5, 5 and 6 s in a session amongst normal training delay trials. The generalisation functions had a slight peak around 2 s. After further training, a second generalisation probe showed a slightly declining function. The probability of reinforcement at the 2 s delay was then dropped to 0.1, so that in the terms of the classical generalisation/peak shift paradigm, 2-s delay trials became S- and 4-s delay trials became S+. A third generalisation probe then was conducted. This resulted in a flat function from 0 s to 3 s, and a large, clear peak in discriminative performance at 4.5 s over all hens. After more of the same differential reinforcement training, a fourth generalisation probe showed a broad curve peaking at 3 s, with minima at 1 s and 6 s and a global maximum at 0 s. Another training condition was then run, with the probability of reinforcement at the 2-s delay dropped to 0, to see if increasing the "aversiveness" of S- would again result in a peak shift. A fifth generalisation probe was then conducted. This showed a sharp decline in discriminability at shorter delays, a dip around 2 s, and a very small area shift beyond 4 s, but no clear peak shift. This was interpreted as being due to overlearning, with the consequences of remembering at S- no longer significantly affecting performance at S+. A final training condition was then run, with S- moved from 2 s to 3 s with zero probability of reinforcement, and for only a short period, to prevent overlearning. It was predicted that this would cause peak shift to re-occur. A sixth generalisation probe was then conducted. This found a further decline in discriminability at shorter delays, a shift in the dip from 2 s to 3 s, and a large, clear peak at 4.5 s. This demonstration of peak shift in a remembering process would not have been predicted by any traditional theory of memory, but strongly supports the conception of remembering as discriminative behaviour along the stimulus dimension of time.

year: 2003

title: An outsider's guide to public oral history in New Zealand

authors: Mahuika, Nepia

subjects: Oral history

abstract: At the beginning of this century, public history in New Zealand was considered a ‘new term’ in historical practice, described as crucial in both ‘the emergence of professional history writing’ and the assertion of ‘cultural nationalism.’¹ In the past decade, scholars here have highlighted its breadth and significance in ‘the employment of historians and the historical method outside academia; in government, private companies, the media, historical societies and museums, as well as those working in private practice.’² Oral history has also become a significant part of public history’s nation-making, key in the collecting of exceptional and ‘ordinary’ public voices.³ For Māori, current definitions of oral and public history are problematic because, as this essay suggests, both are constructed within Pākehā-centric perspectives of history, tradition, orality and what counts as ‘public.’ Public history has been called a ‘slippery process’, often shaped in a contrast between ‘people’s history’ and a ‘search for social cohesion’.4 This search for ‘cohesion’ is a familiar colonial refrain that fuels a healthy native scepticism of public history as yet another settler-centric invention that keeps us on the outside. This essay considers the ways in which public oral history in New Zealand is articulated, noting how this is done within narrow definitions and binaries that displace, ignore, or distort, indigenous perspectives. It suggests a rethinking of oral history as a movement beyond current binaries in the field, and advocates a widening of the meaning of oral sources, methods and politics, in order to include indigenous definitions as legitimately oral and public. This analysis is decolonial, not because it seeks an eradication of nationalism, but because it seeks to disrupt colonial-centric meanings of oral and public history by recentering Māori perspectives as legitimate to the New Zealand public oral history vernacular.

text: An outsider's guide to public oral history in New Zealand At the beginning of this century, public history in New Zealand was considered a ‘new term’ in historical practice, described as crucial in both ‘the emergence of professional history writing’ and the assertion of ‘cultural nationalism.’¹ In the past decade, scholars here have highlighted its breadth and significance in ‘the employment of historians and the historical method outside academia; in government, private companies, the media, historical societies and museums, as well as those working in private practice.’² Oral history has also become a significant part of public history’s nation-making, key in the collecting of exceptional and ‘ordinary’ public voices.³ For Māori, current definitions of oral and public history are problematic because, as this essay suggests, both are constructed within Pākehā-centric perspectives of history, tradition, orality and what counts as ‘public.’ Public history has been called a ‘slippery process’, often shaped in a contrast between ‘people’s history’ and a ‘search for social cohesion’.4 This search for ‘cohesion’ is a familiar colonial refrain that fuels a healthy native scepticism of public history as yet another settler-centric invention that keeps us on the outside. This essay considers the ways in which public oral history in New Zealand is articulated, noting how this is done within narrow definitions and binaries that displace, ignore, or distort, indigenous perspectives. It suggests a rethinking of oral history as a movement beyond current binaries in the field, and advocates a widening of the meaning of oral sources, methods and politics, in order to include indigenous definitions as legitimately oral and public. This analysis is decolonial, not because it seeks an eradication of nationalism, but because it seeks to disrupt colonial-centric meanings of oral and public history by recentering Māori perspectives as legitimate to the New Zealand public oral history vernacular.

year: 2017