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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

Spatial mapping of EC spontaneous activity reveals severe reduction in BB activation vs. LE.A significant decrease in the overall activation intensity (A) of spontaneous events is apparent in BB slices. The intensity of EC activation was calculated as the percentage of total EC pixels active above a threshold value during each coordinated event. B quantifies the localization of activity within EC in terms of the relative activation of lateral vs. medial pixels. Activation is uniform throughout EC in LE but biased in favor of lateral activation in BB. *** p<0.001, ****, p< 0.0001. two-tailed t-test (n’s: LE = 10 slices (7 pups); BB = 6 slices (6 pups)). C shows representative composite images illustrating the activated pixels (greens and reds in pseudocolor overlay shown on right) in a slice from each strain. HC, hippocampus; EC, entorhinal cortex; In every slice medial is down, posterior is right.
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pone.0131259.g004: Spatial mapping of EC spontaneous activity reveals severe reduction in BB activation vs. LE.A significant decrease in the overall activation intensity (A) of spontaneous events is apparent in BB slices. The intensity of EC activation was calculated as the percentage of total EC pixels active above a threshold value during each coordinated event. B quantifies the localization of activity within EC in terms of the relative activation of lateral vs. medial pixels. Activation is uniform throughout EC in LE but biased in favor of lateral activation in BB. *** p<0.001, ****, p< 0.0001. two-tailed t-test (n’s: LE = 10 slices (7 pups); BB = 6 slices (6 pups)). C shows representative composite images illustrating the activated pixels (greens and reds in pseudocolor overlay shown on right) in a slice from each strain. HC, hippocampus; EC, entorhinal cortex; In every slice medial is down, posterior is right.

Mentions: Activation in BB slices registered the most severe evidence of depression relative to LE when assessed in terms of the fraction of pixels active above a threshold level. With a mean activation of 4.14% (± 3.11) this parameter in BB slices registered at a mere 7.2% that of LE slices, where activation averaged 57.26% ± 7.99; (p = 0.0003, two-tailed t-test) (Fig 4A). Even compared to W and SD, which had depressed values for this parameter relative to LE, the BB slices were further depressed by approximately 50%.


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

Peinado A, Abrams CK - PLoS ONE (2015)

Spatial mapping of EC spontaneous activity reveals severe reduction in BB activation vs. LE.A significant decrease in the overall activation intensity (A) of spontaneous events is apparent in BB slices. The intensity of EC activation was calculated as the percentage of total EC pixels active above a threshold value during each coordinated event. B quantifies the localization of activity within EC in terms of the relative activation of lateral vs. medial pixels. Activation is uniform throughout EC in LE but biased in favor of lateral activation in BB. *** p<0.001, ****, p< 0.0001. two-tailed t-test (n’s: LE = 10 slices (7 pups); BB = 6 slices (6 pups)). C shows representative composite images illustrating the activated pixels (greens and reds in pseudocolor overlay shown on right) in a slice from each strain. HC, hippocampus; EC, entorhinal cortex; In every slice medial is down, posterior is right.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476761&req=5

pone.0131259.g004: Spatial mapping of EC spontaneous activity reveals severe reduction in BB activation vs. LE.A significant decrease in the overall activation intensity (A) of spontaneous events is apparent in BB slices. The intensity of EC activation was calculated as the percentage of total EC pixels active above a threshold value during each coordinated event. B quantifies the localization of activity within EC in terms of the relative activation of lateral vs. medial pixels. Activation is uniform throughout EC in LE but biased in favor of lateral activation in BB. *** p<0.001, ****, p< 0.0001. two-tailed t-test (n’s: LE = 10 slices (7 pups); BB = 6 slices (6 pups)). C shows representative composite images illustrating the activated pixels (greens and reds in pseudocolor overlay shown on right) in a slice from each strain. HC, hippocampus; EC, entorhinal cortex; In every slice medial is down, posterior is right.
Mentions: Activation in BB slices registered the most severe evidence of depression relative to LE when assessed in terms of the fraction of pixels active above a threshold level. With a mean activation of 4.14% (± 3.11) this parameter in BB slices registered at a mere 7.2% that of LE slices, where activation averaged 57.26% ± 7.99; (p = 0.0003, two-tailed t-test) (Fig 4A). Even compared to W and SD, which had depressed values for this parameter relative to LE, the BB slices were further depressed by approximately 50%.

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