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Patterns of Spontaneous Local Network Activity in Developing Cerebral Cortex: Relationship to Adult Cognitive Function.

Peinado A, Abrams CK - PLoS ONE (2015)

Bottom Line: Our results show significant differences in this activity between strains: compared to a high cognitive-performing strain, we consistently found an increase in frequency and decrease in intensity in neonates from three lower performing strains.Activity was most different in one strain considered a model of schizophrenia-like psychopathology.Our results further suggest that the strength of dopaminergic signaling, by setting the balance between excitation and inhibition, is a potential underlying mechanism that could explain the observed differences in early spontaneous activity patterns.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York, United States of America.

ABSTRACT
Detecting neurodevelopμental disorders of cognition at the earliest possible stages could assist in understanding them mechanistically and ultimately in treating them. Finding early physiological predictors that could be visualized with functional neuroimaging would represent an important advance in this regard. We hypothesized that one potential source of physiological predictors is the spontaneous local network activity prominent during specific periods in development. To test this we used calcium imaging in brain slices and analyzed variations in the frequency and intensity of this early activity in one area, the entorhinal cortex (EC), in order to correlate early activity with level of cognitive function later in life. We focused on EC because of its known role in different types of cognitive processes and because it is an area where spontaneous activity is prominent during early postnatal development in rodent models of cortical development. Using rat strains (Long-Evans, Wistar, Sprague-Dawley and Brattleboro) known to differ in cognitive performance in adulthood we asked whether neonatal animals exhibit corresponding strain-related differences in EC spontaneous activity. Our results show significant differences in this activity between strains: compared to a high cognitive-performing strain, we consistently found an increase in frequency and decrease in intensity in neonates from three lower performing strains. Activity was most different in one strain considered a model of schizophrenia-like psychopathology. While we cannot necessarily infer a causal relationship between early activity and adult cognition our findings suggest that the pattern of spontaneous activity in development could be an early predictor of a developmental trajectory advancing toward sub-optimal cognitive performance in adulthood. Our results further suggest that the strength of dopaminergic signaling, by setting the balance between excitation and inhibition, is a potential underlying mechanism that could explain the observed differences in early spontaneous activity patterns.

No MeSH data available.


Related in: MedlinePlus

Temporal dynamics of EC spontaneous activity reveals reduced activation in BB relative to LE.A significant increase in the frequency (A) of spontaneous events is apparent in BB slices. In contrast, the intensity of activation (B) as measured by the maximal rate of change in the calcium signal at the onset of each event is significantly reduced in the low performing strain. The coefficient of variation (CV) in the activation intensity of BB was not significantly increased over that of LE (C), demonstrating no increased event-to-event variability in extent of network recruitment. In all cases data are expressed as mean ± SEM. Event variability is based on CVs computed using all events recorded during a calcium imaging sequence. ** p<0.01; ****, p< 0.0001. two-tailed t-test (n’s: LE = 10 slices (7 pups); BB = 6 slices (6 pups)). D shows representative traces of the calcium-dependent fluorescence over time taken from active areas of EC in each strain.
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pone.0131259.g003: Temporal dynamics of EC spontaneous activity reveals reduced activation in BB relative to LE.A significant increase in the frequency (A) of spontaneous events is apparent in BB slices. In contrast, the intensity of activation (B) as measured by the maximal rate of change in the calcium signal at the onset of each event is significantly reduced in the low performing strain. The coefficient of variation (CV) in the activation intensity of BB was not significantly increased over that of LE (C), demonstrating no increased event-to-event variability in extent of network recruitment. In all cases data are expressed as mean ± SEM. Event variability is based on CVs computed using all events recorded during a calcium imaging sequence. ** p<0.01; ****, p< 0.0001. two-tailed t-test (n’s: LE = 10 slices (7 pups); BB = 6 slices (6 pups)). D shows representative traces of the calcium-dependent fluorescence over time taken from active areas of EC in each strain.

Mentions: In the second part of this study we compared EC activity in slices from the Brattleboro strain (BB) to slices from LE, the control parental strain. BB is a naturally-occurring mutant of the LE strain lacking the neuropeptide arginine-vasopressin (AVP) in the central nervous system. Studies have characterized this strain as a useful model for schizophrenia-like pathology and have demonstrated restoration of normal behavior by the atypical antipsychotic, clozapine [27]. We measured the same parameters described above. Our results show that the EC activation pattern in BB was very significantly different from that of its parent strain (Fig 3). This difference can be summarized as a generalized depression of activity, albeit with a significant increase in event frequency (LE: 0.41 ± 0.05 events/min; BB: 0.80 ± 0.12 events/min; p = 0.04, two-tailed t-test) (Fig 3A). Although higher than LE, this frequency of activation was significantly below that observed in both SD and W.


Patterns of Spontaneous Local Network Activity in Developing Cerebral Cortex: Relationship to Adult Cognitive Function.

Peinado A, Abrams CK - PLoS ONE (2015)

Temporal dynamics of EC spontaneous activity reveals reduced activation in BB relative to LE.A significant increase in the frequency (A) of spontaneous events is apparent in BB slices. In contrast, the intensity of activation (B) as measured by the maximal rate of change in the calcium signal at the onset of each event is significantly reduced in the low performing strain. The coefficient of variation (CV) in the activation intensity of BB was not significantly increased over that of LE (C), demonstrating no increased event-to-event variability in extent of network recruitment. In all cases data are expressed as mean ± SEM. Event variability is based on CVs computed using all events recorded during a calcium imaging sequence. ** p<0.01; ****, p< 0.0001. two-tailed t-test (n’s: LE = 10 slices (7 pups); BB = 6 slices (6 pups)). D shows representative traces of the calcium-dependent fluorescence over time taken from active areas of EC in each strain.
© Copyright Policy
Related In: Results  -  Collection

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pone.0131259.g003: Temporal dynamics of EC spontaneous activity reveals reduced activation in BB relative to LE.A significant increase in the frequency (A) of spontaneous events is apparent in BB slices. In contrast, the intensity of activation (B) as measured by the maximal rate of change in the calcium signal at the onset of each event is significantly reduced in the low performing strain. The coefficient of variation (CV) in the activation intensity of BB was not significantly increased over that of LE (C), demonstrating no increased event-to-event variability in extent of network recruitment. In all cases data are expressed as mean ± SEM. Event variability is based on CVs computed using all events recorded during a calcium imaging sequence. ** p<0.01; ****, p< 0.0001. two-tailed t-test (n’s: LE = 10 slices (7 pups); BB = 6 slices (6 pups)). D shows representative traces of the calcium-dependent fluorescence over time taken from active areas of EC in each strain.
Mentions: In the second part of this study we compared EC activity in slices from the Brattleboro strain (BB) to slices from LE, the control parental strain. BB is a naturally-occurring mutant of the LE strain lacking the neuropeptide arginine-vasopressin (AVP) in the central nervous system. Studies have characterized this strain as a useful model for schizophrenia-like pathology and have demonstrated restoration of normal behavior by the atypical antipsychotic, clozapine [27]. We measured the same parameters described above. Our results show that the EC activation pattern in BB was very significantly different from that of its parent strain (Fig 3). This difference can be summarized as a generalized depression of activity, albeit with a significant increase in event frequency (LE: 0.41 ± 0.05 events/min; BB: 0.80 ± 0.12 events/min; p = 0.04, two-tailed t-test) (Fig 3A). Although higher than LE, this frequency of activation was significantly below that observed in both SD and W.

Bottom Line: Our results show significant differences in this activity between strains: compared to a high cognitive-performing strain, we consistently found an increase in frequency and decrease in intensity in neonates from three lower performing strains.Activity was most different in one strain considered a model of schizophrenia-like psychopathology.Our results further suggest that the strength of dopaminergic signaling, by setting the balance between excitation and inhibition, is a potential underlying mechanism that could explain the observed differences in early spontaneous activity patterns.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology and Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York, United States of America.

ABSTRACT
Detecting neurodevelopμental disorders of cognition at the earliest possible stages could assist in understanding them mechanistically and ultimately in treating them. Finding early physiological predictors that could be visualized with functional neuroimaging would represent an important advance in this regard. We hypothesized that one potential source of physiological predictors is the spontaneous local network activity prominent during specific periods in development. To test this we used calcium imaging in brain slices and analyzed variations in the frequency and intensity of this early activity in one area, the entorhinal cortex (EC), in order to correlate early activity with level of cognitive function later in life. We focused on EC because of its known role in different types of cognitive processes and because it is an area where spontaneous activity is prominent during early postnatal development in rodent models of cortical development. Using rat strains (Long-Evans, Wistar, Sprague-Dawley and Brattleboro) known to differ in cognitive performance in adulthood we asked whether neonatal animals exhibit corresponding strain-related differences in EC spontaneous activity. Our results show significant differences in this activity between strains: compared to a high cognitive-performing strain, we consistently found an increase in frequency and decrease in intensity in neonates from three lower performing strains. Activity was most different in one strain considered a model of schizophrenia-like psychopathology. While we cannot necessarily infer a causal relationship between early activity and adult cognition our findings suggest that the pattern of spontaneous activity in development could be an early predictor of a developmental trajectory advancing toward sub-optimal cognitive performance in adulthood. Our results further suggest that the strength of dopaminergic signaling, by setting the balance between excitation and inhibition, is a potential underlying mechanism that could explain the observed differences in early spontaneous activity patterns.

No MeSH data available.


Related in: MedlinePlus