Eric Hanse - Academia.edu (original) (raw)

Papers by Eric Hanse

Frontiers in Cellular Neuroscience, 2016

[This corrects the article on p. 54 in vol. 10, PMID: 26973467.].

Scientific Reports, 2016

Amyloid precursor protein (APP) and its cleavage product amyloid β (Aβ) have been thoroughly stud... more Amyloid precursor protein (APP) and its cleavage product amyloid β (Aβ) have been thoroughly studied in Alzheimer's disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development. Here, we investigated expression and proteolytic processing of APP during differentiation of human iPSCs towards cortical neurons over a 100-day period. APP expression remained stable during neuronal differentiation, whereas APP processing changed. α-Cleaved soluble APP (sAPPα) was secreted early during differentiation, from neuronal progenitors, while β-cleaved soluble APP (sAPPβ) was first secreted after deep-layer neurons had formed. Short Aβ peptides, including Aβ1-15/16, peaked during the progenitor stage, while processing shifted towards longer peptides, such as Aβ1-40/42, when post-mitotic neurons appeared. This indicates that APP processing is regulated throughout differentiation of cortical neurons and that amyloidogenic APP processing, as reflected by Aβ1-40/42, is associated with mature neuronal phenotypes.

The Journal of Physiology, Mar 1, 2001

Abstract1Quantal variability was determined at glutamatergic synapses in the neonatal (postnatal ... more Abstract1Quantal variability was determined at glutamatergic synapses in the neonatal (postnatal days 1-7) rat hippocampal slice preparation. Synaptic AMPA and NMDA quantal EPSCs were recorded from CA1 pyramidal neurones using the whole-cell, or perforated, patch-clamp technique.2Release was evoked by minimal stimulation using brief trains (10 impulses, 50 Hz), and various tests ascertained that this stimulation activated single release sites releasing single vesicles.3Both AMPA and NMDA quantal responses at a given release site varied considerably in magnitude, the coefficient of variation (CV) among the synapses averaging 0.39 and 0.30, respectively. This variability differed among the synapses, from 0.2 to 0.7, and 0.10 to 0.50, respectively, and CV values of AMPA responses co-varied with those of the NMDA responses.4Both for AMPA and NMDA, low CV values were associated with a Gaussian distribution of EPSC peak values, whereas synapses with high CV values displayed distributions skewed towards lower values.5Analysis of successive NMDA responses during a train revealed a considerable degree of non-saturation of NMDA receptors by a single vesicle.6The results are compatible with a quantal variability based, to a large extent, on non-saturated AMPA and NMDA responses fluctuating as a function of the amount of transmitter released from each vesicle.

Neuroscience, Feb 1, 2003

Correlated pre- and postsynaptic activity is thought to promote maturation of excitatory synapses... more Correlated pre- and postsynaptic activity is thought to promote maturation of excitatory synapses in the developing brain by directing AMPA receptors to pure NMDA synapses. However, this hypothesis has not been tested in vivo. Here, we have performed such test by inhibiting correlated neural activity in vivo using a single injection of tetanus toxin into the rat hippocampal CA1 area at postnatal day 1. When examined in the acute slice preparation (1–7 days post-injection), there was a strong reduction, down to 20% of control level, in the frequency of glutamatergic and GABAergic spontaneous postsynaptic currents (sPSCs). This activity deprivation led to a growth retardation of CA1 pyramidal neurons and to markedly faster decay kinetics of NMDA sPCSs. However, it did not alter the relationship between AMPA and NMDA sPSCs with respect to either their frequency or amplitude. Thus, although critical for certain aspects of neuronal development, correlated neural activity in the neonatal hippocampus does not seem to promote incorporation of AMPA receptors at pure NMDA synapses.

Exp Gerontol, 2010

Intense research during the past decade has aimed at dissecting the molecular pathogenesis of Alz... more Intense research during the past decade has aimed at dissecting the molecular pathogenesis of Alzheimer’s disease (AD). Primarily, the focus has been directed towards brain amyloid pathology and its relation to synaptic and neuronal loss. Clearly, AD is associated with accumulation of amyloid β (Aβ) in the brain. Further, the results of many experimental studies suggest that certain forms of Aβ may act as initiators in the disease process with potent toxic effects at the synaptic level. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include secreted Aβ and amyloid precursor protein (APP) isoforms, Aβ oligomers and β-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on CSF and plasma Aβ-related biomarkers for AD and how they may reflect pathogenic changes in AD-affected neuronal networks. We also consider their usefulness in clinical practice and in clinical trials.

Neuroscience Research, Jul 31, 1994

Frontiers in Cellular Neuroscience, 2016

For decades it has been hypothesized that molecules within the cerebrospinal fluid (CSF) diffuse ... more For decades it has been hypothesized that molecules within the cerebrospinal fluid (CSF) diffuse into the brain parenchyma and influence the function of neurons. However, the functional consequences of CSF on neuronal circuits are largely unexplored and unknown. A major reason for this is the absence of appropriate neuronal in vitro model systems, and it is uncertain if neurons cultured in pure CSF survive and preserve electrophysiological functionality in vitro. In this article, we present an approach to address how human CSF (hCSF) influences neuronal circuits in vitro. We validate our approach by comparing the morphology, viability, and electrophysiological function of single neurons and at the network level in rat organotypic slice and primary neuronal cultures cultivated either in hCSF or in defined standard culture media. Our results demonstrate that rodent hippocampal slices and primary neurons cultured in hCSF maintain neuronal morphology and preserve synaptic transmission. Importantly, we show that hCSF increases neuronal viability and the number of electrophysiologically active neurons in comparison to the culture media. In summary, our data indicate that hCSF represents a physiological environment for neurons in vitro and a superior culture condition compared to the defined standard media. Moreover, this experimental approach paves the way to assess the functional consequences of CSF on neuronal circuits as well as suggesting a novel strategy for central nervous system (CNS) disease modeling.

Neuroscience, 1998

Brief elevation in postsynaptic calcium in hippocampal CA1 neurons leads to prolonged changes in ... more Brief elevation in postsynaptic calcium in hippocampal CA1 neurons leads to prolonged changes in synaptic strength. The calcium may enter the postsynaptic neuron via different routes, such as voltage-gated calcium channels or glutamate receptor channels of N-methyl-d-aspartate type, and/or be released from intracellular stores. The manner in which the synapse is altered, leading to the expression of an enhanced/depressed synaptic strength, is still unclear. The present study, performed using whole-cell recording from CA1 pyramidal cells of three- to five-week-old guinea-pigs, shows that postsynaptic depolarization alone, allowing for calcium influx through voltage-gated calcium channels, leads to a synaptic potentiation characterized by an altered time-course of the evoked excitatory synaptic response, an unaltered coefficient of variation of that response and a decreased paired-pulse facilitation likely related to a postsynaptic mechanism. These characteristics contrasted with those of long-term potentiation induced via activation of N-methyl-d-aspartate receptor channels, where the time-course was unaltered, the coefficient of variation was decreased and no change in paired-pulse facilitation was observed.Synapses can thus have mechanistically separate, but co-existent, potentiations of synaptic transmission initiated from separate sources for postsynaptic calcium.

The Journal of Physiology, 2015

GABAergic interneurons intricately regulate the activity of hippocampal and neocortical networks.... more GABAergic interneurons intricately regulate the activity of hippocampal and neocortical networks. Their function in vivo is likely to be tuned by neuromodulatory substances in brain extracellular fluid. However, in vitro investigations of GABAergic interneuron function do not account for such effects, as neurons are kept in artificial extracellular fluid. To examine the neuromodulatory influence of brain extracellular fluid on GABAergic activity, we recorded from fast-spiking and non-fast-spiking CA1 interneurons, as well as from pyramidal cells, in the presence of human cerebrospinal fluid (hCSF), using a matched artificial cerebrospinal (aCSF) fluid as control. We found that hCSF increased the frequency of spontaneous firing more than twofold in the two groups of interneurons, and more than fourfold in CA1 pyramidal cells. hCSF did not affect the resting membrane potential of CA1 interneurons but caused depolarization in pyramidal cells. The increased excitability of interneurons and pyramidal cells was accompanied by reductions in afterhyperpolarization amplitudes and a left-shift in the frequency-current relationships. Our results suggest that ambient concentrations of neuromodulators in the brain extracellular fluid powerfully influence the excitability of neuronal networks. This article is protected by copyright. All rights reserved.

Journal of Tissue Engineering and Regenerative Medicine, 2012

European Journal of Neuroscience, May 1, 2009

Glutamate transmission to gamma-aminobutyric acid (GABA)ergic interneurons and to principal neuro... more Glutamate transmission to gamma-aminobutyric acid (GABA)ergic interneurons and to principal neurons differs in various important respects. Whether these differences exist from an early developmental stage, or result from differential development from a more common state, is unclear. In the hippocampal CA1 area, glutamate transmission to the developing, but not to the adult, principal neurons is characterized by the presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) silent synapses and of AMPA silencing induced by test pulse stimulation (0.03-1 Hz). In the present study, we examined whether this developmental difference in AMPA signaling is also true for glutamate transmission to CA1 stratum radiatum interneurons. We found that AMPA silent synapses onto these interneurons also exist, and that they can be generated by test pulse stimulation. In marked contrast to AMPA silencing in principal neurons, AMPA silencing in interneurons was not developmentally restricted, but was observed to the same extent after the first postnatal month as in the second postnatal week. In addition, we found that glutamate synapses onto these interneurons can also be N-methyl-d-aspartate (NMDA)-silent, that is, only AMPA-signaling. After test pulse stimulation, the AMPA-silent, the NMDA-silent and the AMPA/NMDA-signaling synapses onto the developing interneurons were estimated to be about equally frequent. These results highlight a diversity of glutamate signaling to CA1 stratum radiatum interneurons, and they indicate that the glutamate synapses onto pyramidal neurons and to interneurons can mature differentially.

The Journal of Neuroscience the Official Journal of the Society For Neuroscience, Aug 1, 1994

European Journal of Neuroscience, 2015

In contrast to tonic extrasynaptic γ-aminobutyric acid (GABA)A receptor-mediated signalling, the ... more In contrast to tonic extrasynaptic γ-aminobutyric acid (GABA)A receptor-mediated signalling, the physiological significance of tonic extrasynaptic N-methyl-d-aspartate (NMDA) receptor (NMDAR)-mediated signalling remains uncertain. In this study, reversible open-channel blockers of NMDARs, memantine and phencyclidine (PCP) were used as tools to examine tonic NMDAR-mediated signalling in rat hippocampal slices. Memantine in concentrations up to 10 μm had no effect on synaptically evoked NMDAR-mediated responses in pyramidal neurons or GABAergic interneurons. On the other hand, 10 μm memantine reduced tonic NMDAR-mediated currents in GABAergic interneurons by approximately 50%. These tonic NMDAR-mediated currents in interneurons contributed significantly to the excitability of the interneurons as 10 μm memantine reduced the disynaptic inhibitory postsynaptic current in pyramidal cells by about 50%. Moreover, 10 μm memantine, but also PCP in concentrations ≤ 1 μm, increased the magnitude of the population spike, likely because of disinhibition. The relatively higher impact of tonic NMDAR-mediated signalling in interneurons was at least partly explained by the expression of GluN2D-containing NMDARs, which was not observed in mature pyramidal cells. The current results are consistent with the idea that low doses of readily reversible NMDAR open-channel blockers preferentially inhibit tonically active extrasynaptic NMDARs, and they suggest that tonically active NMDARs contribute more prominently to the intrinsic excitation in GABAergic interneurons than in pyramidal cells. It is proposed that this specific difference between interneurons and pyramidal cells can explain the disinhibition caused by the Alzheimer's disease medication memantine.

Medical Teacher, 2011

Undergraduate medical education in Sweden has moved from nationally regulated, subject-based cour... more Undergraduate medical education in Sweden has moved from nationally regulated, subject-based courses to programmes integrated either around organ systems or physiological and patho-physiological processes, or organised around basic medical science in conjunction with clinical specialities, with individual profiles at the seven medical schools. The national regulations are restricted to overall academic and professional outcomes. The 5½ year long university undergraduate curriculum is followed by a mandatory 18 months internship, delivered by the County Councils. While quality control and accreditation for the university curriculum is provided by the Swedish National Agency for Higher Education, no such formal control exists for the internship; undergraduate medical education is therefore in conflict with EU directives from 2005. The Government is expected to move towards 6 years long university undergraduate programmes, leading to licence, which will facilitate international mobility of both Swedish and foreign medical students and doctors. Ongoing academic development of undergraduate education is strengthened by the Bologna process. It includes outcome (competence)-based curricula, university Masters level complying with international standards, progression of competence throughout the curriculum, student directed learning, active participation and roles in practical clinical education and a national assessment model to assure professional competence. In the near future, the dimensioning of Swedish undergraduate education is likely to be decided more by international demands and aspects of quality than by national demands for doctors.

Frontiers in Cellular Neuroscience, 2016

[This corrects the article on p. 54 in vol. 10, PMID: 26973467.].

Scientific Reports, 2016

Amyloid precursor protein (APP) and its cleavage product amyloid β (Aβ) have been thoroughly stud... more Amyloid precursor protein (APP) and its cleavage product amyloid β (Aβ) have been thoroughly studied in Alzheimer's disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development. Here, we investigated expression and proteolytic processing of APP during differentiation of human iPSCs towards cortical neurons over a 100-day period. APP expression remained stable during neuronal differentiation, whereas APP processing changed. α-Cleaved soluble APP (sAPPα) was secreted early during differentiation, from neuronal progenitors, while β-cleaved soluble APP (sAPPβ) was first secreted after deep-layer neurons had formed. Short Aβ peptides, including Aβ1-15/16, peaked during the progenitor stage, while processing shifted towards longer peptides, such as Aβ1-40/42, when post-mitotic neurons appeared. This indicates that APP processing is regulated throughout differentiation of cortical neurons and that amyloidogenic APP processing, as reflected by Aβ1-40/42, is associated with mature neuronal phenotypes.

The Journal of Physiology, Mar 1, 2001

Abstract1Quantal variability was determined at glutamatergic synapses in the neonatal (postnatal ... more Abstract1Quantal variability was determined at glutamatergic synapses in the neonatal (postnatal days 1-7) rat hippocampal slice preparation. Synaptic AMPA and NMDA quantal EPSCs were recorded from CA1 pyramidal neurones using the whole-cell, or perforated, patch-clamp technique.2Release was evoked by minimal stimulation using brief trains (10 impulses, 50 Hz), and various tests ascertained that this stimulation activated single release sites releasing single vesicles.3Both AMPA and NMDA quantal responses at a given release site varied considerably in magnitude, the coefficient of variation (CV) among the synapses averaging 0.39 and 0.30, respectively. This variability differed among the synapses, from 0.2 to 0.7, and 0.10 to 0.50, respectively, and CV values of AMPA responses co-varied with those of the NMDA responses.4Both for AMPA and NMDA, low CV values were associated with a Gaussian distribution of EPSC peak values, whereas synapses with high CV values displayed distributions skewed towards lower values.5Analysis of successive NMDA responses during a train revealed a considerable degree of non-saturation of NMDA receptors by a single vesicle.6The results are compatible with a quantal variability based, to a large extent, on non-saturated AMPA and NMDA responses fluctuating as a function of the amount of transmitter released from each vesicle.

Neuroscience, Feb 1, 2003

Correlated pre- and postsynaptic activity is thought to promote maturation of excitatory synapses... more Correlated pre- and postsynaptic activity is thought to promote maturation of excitatory synapses in the developing brain by directing AMPA receptors to pure NMDA synapses. However, this hypothesis has not been tested in vivo. Here, we have performed such test by inhibiting correlated neural activity in vivo using a single injection of tetanus toxin into the rat hippocampal CA1 area at postnatal day 1. When examined in the acute slice preparation (1–7 days post-injection), there was a strong reduction, down to 20% of control level, in the frequency of glutamatergic and GABAergic spontaneous postsynaptic currents (sPSCs). This activity deprivation led to a growth retardation of CA1 pyramidal neurons and to markedly faster decay kinetics of NMDA sPCSs. However, it did not alter the relationship between AMPA and NMDA sPSCs with respect to either their frequency or amplitude. Thus, although critical for certain aspects of neuronal development, correlated neural activity in the neonatal hippocampus does not seem to promote incorporation of AMPA receptors at pure NMDA synapses.

Exp Gerontol, 2010

Intense research during the past decade has aimed at dissecting the molecular pathogenesis of Alz... more Intense research during the past decade has aimed at dissecting the molecular pathogenesis of Alzheimer’s disease (AD). Primarily, the focus has been directed towards brain amyloid pathology and its relation to synaptic and neuronal loss. Clearly, AD is associated with accumulation of amyloid β (Aβ) in the brain. Further, the results of many experimental studies suggest that certain forms of Aβ may act as initiators in the disease process with potent toxic effects at the synaptic level. Molecular aberrations in the AD brain are reflected in the cerebrospinal fluid (CSF). Core CSF biomarkers include secreted Aβ and amyloid precursor protein (APP) isoforms, Aβ oligomers and β-site APP-cleaving enzyme 1 (BACE1). This article reviews recent research advances on CSF and plasma Aβ-related biomarkers for AD and how they may reflect pathogenic changes in AD-affected neuronal networks. We also consider their usefulness in clinical practice and in clinical trials.

Neuroscience Research, Jul 31, 1994

Frontiers in Cellular Neuroscience, 2016

For decades it has been hypothesized that molecules within the cerebrospinal fluid (CSF) diffuse ... more For decades it has been hypothesized that molecules within the cerebrospinal fluid (CSF) diffuse into the brain parenchyma and influence the function of neurons. However, the functional consequences of CSF on neuronal circuits are largely unexplored and unknown. A major reason for this is the absence of appropriate neuronal in vitro model systems, and it is uncertain if neurons cultured in pure CSF survive and preserve electrophysiological functionality in vitro. In this article, we present an approach to address how human CSF (hCSF) influences neuronal circuits in vitro. We validate our approach by comparing the morphology, viability, and electrophysiological function of single neurons and at the network level in rat organotypic slice and primary neuronal cultures cultivated either in hCSF or in defined standard culture media. Our results demonstrate that rodent hippocampal slices and primary neurons cultured in hCSF maintain neuronal morphology and preserve synaptic transmission. Importantly, we show that hCSF increases neuronal viability and the number of electrophysiologically active neurons in comparison to the culture media. In summary, our data indicate that hCSF represents a physiological environment for neurons in vitro and a superior culture condition compared to the defined standard media. Moreover, this experimental approach paves the way to assess the functional consequences of CSF on neuronal circuits as well as suggesting a novel strategy for central nervous system (CNS) disease modeling.

Neuroscience, 1998

Brief elevation in postsynaptic calcium in hippocampal CA1 neurons leads to prolonged changes in ... more Brief elevation in postsynaptic calcium in hippocampal CA1 neurons leads to prolonged changes in synaptic strength. The calcium may enter the postsynaptic neuron via different routes, such as voltage-gated calcium channels or glutamate receptor channels of N-methyl-d-aspartate type, and/or be released from intracellular stores. The manner in which the synapse is altered, leading to the expression of an enhanced/depressed synaptic strength, is still unclear. The present study, performed using whole-cell recording from CA1 pyramidal cells of three- to five-week-old guinea-pigs, shows that postsynaptic depolarization alone, allowing for calcium influx through voltage-gated calcium channels, leads to a synaptic potentiation characterized by an altered time-course of the evoked excitatory synaptic response, an unaltered coefficient of variation of that response and a decreased paired-pulse facilitation likely related to a postsynaptic mechanism. These characteristics contrasted with those of long-term potentiation induced via activation of N-methyl-d-aspartate receptor channels, where the time-course was unaltered, the coefficient of variation was decreased and no change in paired-pulse facilitation was observed.Synapses can thus have mechanistically separate, but co-existent, potentiations of synaptic transmission initiated from separate sources for postsynaptic calcium.

The Journal of Physiology, 2015

GABAergic interneurons intricately regulate the activity of hippocampal and neocortical networks.... more GABAergic interneurons intricately regulate the activity of hippocampal and neocortical networks. Their function in vivo is likely to be tuned by neuromodulatory substances in brain extracellular fluid. However, in vitro investigations of GABAergic interneuron function do not account for such effects, as neurons are kept in artificial extracellular fluid. To examine the neuromodulatory influence of brain extracellular fluid on GABAergic activity, we recorded from fast-spiking and non-fast-spiking CA1 interneurons, as well as from pyramidal cells, in the presence of human cerebrospinal fluid (hCSF), using a matched artificial cerebrospinal (aCSF) fluid as control. We found that hCSF increased the frequency of spontaneous firing more than twofold in the two groups of interneurons, and more than fourfold in CA1 pyramidal cells. hCSF did not affect the resting membrane potential of CA1 interneurons but caused depolarization in pyramidal cells. The increased excitability of interneurons and pyramidal cells was accompanied by reductions in afterhyperpolarization amplitudes and a left-shift in the frequency-current relationships. Our results suggest that ambient concentrations of neuromodulators in the brain extracellular fluid powerfully influence the excitability of neuronal networks. This article is protected by copyright. All rights reserved.

Journal of Tissue Engineering and Regenerative Medicine, 2012

European Journal of Neuroscience, May 1, 2009

Glutamate transmission to gamma-aminobutyric acid (GABA)ergic interneurons and to principal neuro... more Glutamate transmission to gamma-aminobutyric acid (GABA)ergic interneurons and to principal neurons differs in various important respects. Whether these differences exist from an early developmental stage, or result from differential development from a more common state, is unclear. In the hippocampal CA1 area, glutamate transmission to the developing, but not to the adult, principal neurons is characterized by the presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) silent synapses and of AMPA silencing induced by test pulse stimulation (0.03-1 Hz). In the present study, we examined whether this developmental difference in AMPA signaling is also true for glutamate transmission to CA1 stratum radiatum interneurons. We found that AMPA silent synapses onto these interneurons also exist, and that they can be generated by test pulse stimulation. In marked contrast to AMPA silencing in principal neurons, AMPA silencing in interneurons was not developmentally restricted, but was observed to the same extent after the first postnatal month as in the second postnatal week. In addition, we found that glutamate synapses onto these interneurons can also be N-methyl-d-aspartate (NMDA)-silent, that is, only AMPA-signaling. After test pulse stimulation, the AMPA-silent, the NMDA-silent and the AMPA/NMDA-signaling synapses onto the developing interneurons were estimated to be about equally frequent. These results highlight a diversity of glutamate signaling to CA1 stratum radiatum interneurons, and they indicate that the glutamate synapses onto pyramidal neurons and to interneurons can mature differentially.

The Journal of Neuroscience the Official Journal of the Society For Neuroscience, Aug 1, 1994

European Journal of Neuroscience, 2015

In contrast to tonic extrasynaptic γ-aminobutyric acid (GABA)A receptor-mediated signalling, the ... more In contrast to tonic extrasynaptic γ-aminobutyric acid (GABA)A receptor-mediated signalling, the physiological significance of tonic extrasynaptic N-methyl-d-aspartate (NMDA) receptor (NMDAR)-mediated signalling remains uncertain. In this study, reversible open-channel blockers of NMDARs, memantine and phencyclidine (PCP) were used as tools to examine tonic NMDAR-mediated signalling in rat hippocampal slices. Memantine in concentrations up to 10 μm had no effect on synaptically evoked NMDAR-mediated responses in pyramidal neurons or GABAergic interneurons. On the other hand, 10 μm memantine reduced tonic NMDAR-mediated currents in GABAergic interneurons by approximately 50%. These tonic NMDAR-mediated currents in interneurons contributed significantly to the excitability of the interneurons as 10 μm memantine reduced the disynaptic inhibitory postsynaptic current in pyramidal cells by about 50%. Moreover, 10 μm memantine, but also PCP in concentrations ≤ 1 μm, increased the magnitude of the population spike, likely because of disinhibition. The relatively higher impact of tonic NMDAR-mediated signalling in interneurons was at least partly explained by the expression of GluN2D-containing NMDARs, which was not observed in mature pyramidal cells. The current results are consistent with the idea that low doses of readily reversible NMDAR open-channel blockers preferentially inhibit tonically active extrasynaptic NMDARs, and they suggest that tonically active NMDARs contribute more prominently to the intrinsic excitation in GABAergic interneurons than in pyramidal cells. It is proposed that this specific difference between interneurons and pyramidal cells can explain the disinhibition caused by the Alzheimer's disease medication memantine.

Medical Teacher, 2011

Undergraduate medical education in Sweden has moved from nationally regulated, subject-based cour... more Undergraduate medical education in Sweden has moved from nationally regulated, subject-based courses to programmes integrated either around organ systems or physiological and patho-physiological processes, or organised around basic medical science in conjunction with clinical specialities, with individual profiles at the seven medical schools. The national regulations are restricted to overall academic and professional outcomes. The 5½ year long university undergraduate curriculum is followed by a mandatory 18 months internship, delivered by the County Councils. While quality control and accreditation for the university curriculum is provided by the Swedish National Agency for Higher Education, no such formal control exists for the internship; undergraduate medical education is therefore in conflict with EU directives from 2005. The Government is expected to move towards 6 years long university undergraduate programmes, leading to licence, which will facilitate international mobility of both Swedish and foreign medical students and doctors. Ongoing academic development of undergraduate education is strengthened by the Bologna process. It includes outcome (competence)-based curricula, university Masters level complying with international standards, progression of competence throughout the curriculum, student directed learning, active participation and roles in practical clinical education and a national assessment model to assure professional competence. In the near future, the dimensioning of Swedish undergraduate education is likely to be decided more by international demands and aspects of quality than by national demands for doctors.