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Developmental switch in neurovascular coupling in the immature rodent barrel cortex.

Zehendner CM, Tsohataridis S, Luhmann HJ, Yang JW - PLoS ONE (2013)

Bottom Line: In the mature CNS it is well accepted that cortical sensory processing results in a rise in regional cerebral blood flow (rCBF).In contrast at P30, MUA remains stable during repetitive stimulation and is associated with an increase in rCBF.Further we characterize in both age groups the responses in NVC to single sensory stimuli.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.

ABSTRACT
Neurovascular coupling (NVC) in the adult central nervous system (CNS) is a mechanism that provides regions of the brain with more oxygen and glucose upon increased levels of neural activation. Hemodynamic changes that go along with neural activation evoke a blood oxygen level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) that can be used to study brain activity non-invasively. A correct correlation of the BOLD signal to neural activity is pivotal to understand this signal in neuronal development, health and disease. However, the function of NVC during development is largely unknown. The rodent whisker-to-barrel cortex is an experimentally well established model to study neurovascular interdependences. Using extracellular multi-electrode recordings and laser-Doppler-flowmetry (LDF) we show in the murine barrel cortex of postnatal day 7 (P7) and P30 mice in vivo that NVC undergoes a physiological shift during the first month of life. In the mature CNS it is well accepted that cortical sensory processing results in a rise in regional cerebral blood flow (rCBF). We show in P7 animals that rCBF decreases during prolonged multi-whisker stimulation and goes along with multi unit activity (MUA) fatigue. In contrast at P30, MUA remains stable during repetitive stimulation and is associated with an increase in rCBF. Further we characterize in both age groups the responses in NVC to single sensory stimuli. We suggest that the observed shift in NVC is an important process in cortical development that may be of high relevance for the correct interpretation of brain activity e.g. in fMRI studies of the immature central nervous system (CNS).

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Prolonged multi-whisker stimulation.At P7 prolonged multi-whisker stimulation at 4 Hz resulted in a decline in rCBF. rCBF declined until it reached a plateau and slowly recovered to baseline within 20 - 30 s after the end of stimulation (A 1). In P30 4 Hz stimulation caused a rCBF increase until a plateau was reached and declined after stimulation. In many cases rCBF did not reach baseline levels but remained slightly elevated (B 1). Simultaneous MUA recordings in the barrel cortex of P7 mice demonstrated an initial rise in MUA that decreased during ongoing stimulation (A 2). Note that the baseline MUA after stimulation appears to be reduced compared with MUA before stimulation indicating spontaneous MUAF. At P30 MUA responded in a similar manner as in P7 but the prominent decrease in spontaneous MUA after stimulation was not apparent (B 2). At P7 the MUA increase related to baseline MUA before stimulation was significantly higher than at P30 (C). The average rCBF change during stimulation compared with baseline was also significantly different in both age groups. At P7 rCBF decreased while during stimulation rCBF increased at P30 (D). MUA decrease over stimulation time was significantly higher in P7 compared with P30 (E). In contrast spontaneous MUA before stimulation was higher at P30 compared with P7 (F). Statistical analyses of MUA after stimulation compared with MUA levels before stimulation show a significant reduction in spontaneous MUA following 4 Hz whisker deflection in P7 that is much less pronounced in P30 (G). Red bar indicates 4 Hz stimulation; *** P < 0.001; ** P < 0.01; * P < 0.05. Grey shades in rCBF panels A and B indicate + SEM.
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pone-0080749-g006: Prolonged multi-whisker stimulation.At P7 prolonged multi-whisker stimulation at 4 Hz resulted in a decline in rCBF. rCBF declined until it reached a plateau and slowly recovered to baseline within 20 - 30 s after the end of stimulation (A 1). In P30 4 Hz stimulation caused a rCBF increase until a plateau was reached and declined after stimulation. In many cases rCBF did not reach baseline levels but remained slightly elevated (B 1). Simultaneous MUA recordings in the barrel cortex of P7 mice demonstrated an initial rise in MUA that decreased during ongoing stimulation (A 2). Note that the baseline MUA after stimulation appears to be reduced compared with MUA before stimulation indicating spontaneous MUAF. At P30 MUA responded in a similar manner as in P7 but the prominent decrease in spontaneous MUA after stimulation was not apparent (B 2). At P7 the MUA increase related to baseline MUA before stimulation was significantly higher than at P30 (C). The average rCBF change during stimulation compared with baseline was also significantly different in both age groups. At P7 rCBF decreased while during stimulation rCBF increased at P30 (D). MUA decrease over stimulation time was significantly higher in P7 compared with P30 (E). In contrast spontaneous MUA before stimulation was higher at P30 compared with P7 (F). Statistical analyses of MUA after stimulation compared with MUA levels before stimulation show a significant reduction in spontaneous MUA following 4 Hz whisker deflection in P7 that is much less pronounced in P30 (G). Red bar indicates 4 Hz stimulation; *** P < 0.001; ** P < 0.01; * P < 0.05. Grey shades in rCBF panels A and B indicate + SEM.

Mentions: rCBF recordings in intact skull preparations indicate that the craniotomy in our experimental setup did not affect rCBF measurements. Panel A shows an average 0.1 Hz recording trace from 100 stimulation events of a P7 mouse. In B an average 4 Hz recording is displayed. Note that both traces display similar shapes and characteristics compared with rCBF traces obtained in craniotomy (see Figures 3 and 6). Dashed red line in A: single multi-whisker stimulus, red bar in B: 4 Hz multi-whisker stimulation. Grey shades indicate + SEM. Representative recording traces from 3 P7 animals are displayed.


Developmental switch in neurovascular coupling in the immature rodent barrel cortex.

Zehendner CM, Tsohataridis S, Luhmann HJ, Yang JW - PLoS ONE (2013)

Prolonged multi-whisker stimulation.At P7 prolonged multi-whisker stimulation at 4 Hz resulted in a decline in rCBF. rCBF declined until it reached a plateau and slowly recovered to baseline within 20 - 30 s after the end of stimulation (A 1). In P30 4 Hz stimulation caused a rCBF increase until a plateau was reached and declined after stimulation. In many cases rCBF did not reach baseline levels but remained slightly elevated (B 1). Simultaneous MUA recordings in the barrel cortex of P7 mice demonstrated an initial rise in MUA that decreased during ongoing stimulation (A 2). Note that the baseline MUA after stimulation appears to be reduced compared with MUA before stimulation indicating spontaneous MUAF. At P30 MUA responded in a similar manner as in P7 but the prominent decrease in spontaneous MUA after stimulation was not apparent (B 2). At P7 the MUA increase related to baseline MUA before stimulation was significantly higher than at P30 (C). The average rCBF change during stimulation compared with baseline was also significantly different in both age groups. At P7 rCBF decreased while during stimulation rCBF increased at P30 (D). MUA decrease over stimulation time was significantly higher in P7 compared with P30 (E). In contrast spontaneous MUA before stimulation was higher at P30 compared with P7 (F). Statistical analyses of MUA after stimulation compared with MUA levels before stimulation show a significant reduction in spontaneous MUA following 4 Hz whisker deflection in P7 that is much less pronounced in P30 (G). Red bar indicates 4 Hz stimulation; *** P < 0.001; ** P < 0.01; * P < 0.05. Grey shades in rCBF panels A and B indicate + SEM.
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pone-0080749-g006: Prolonged multi-whisker stimulation.At P7 prolonged multi-whisker stimulation at 4 Hz resulted in a decline in rCBF. rCBF declined until it reached a plateau and slowly recovered to baseline within 20 - 30 s after the end of stimulation (A 1). In P30 4 Hz stimulation caused a rCBF increase until a plateau was reached and declined after stimulation. In many cases rCBF did not reach baseline levels but remained slightly elevated (B 1). Simultaneous MUA recordings in the barrel cortex of P7 mice demonstrated an initial rise in MUA that decreased during ongoing stimulation (A 2). Note that the baseline MUA after stimulation appears to be reduced compared with MUA before stimulation indicating spontaneous MUAF. At P30 MUA responded in a similar manner as in P7 but the prominent decrease in spontaneous MUA after stimulation was not apparent (B 2). At P7 the MUA increase related to baseline MUA before stimulation was significantly higher than at P30 (C). The average rCBF change during stimulation compared with baseline was also significantly different in both age groups. At P7 rCBF decreased while during stimulation rCBF increased at P30 (D). MUA decrease over stimulation time was significantly higher in P7 compared with P30 (E). In contrast spontaneous MUA before stimulation was higher at P30 compared with P7 (F). Statistical analyses of MUA after stimulation compared with MUA levels before stimulation show a significant reduction in spontaneous MUA following 4 Hz whisker deflection in P7 that is much less pronounced in P30 (G). Red bar indicates 4 Hz stimulation; *** P < 0.001; ** P < 0.01; * P < 0.05. Grey shades in rCBF panels A and B indicate + SEM.
Mentions: rCBF recordings in intact skull preparations indicate that the craniotomy in our experimental setup did not affect rCBF measurements. Panel A shows an average 0.1 Hz recording trace from 100 stimulation events of a P7 mouse. In B an average 4 Hz recording is displayed. Note that both traces display similar shapes and characteristics compared with rCBF traces obtained in craniotomy (see Figures 3 and 6). Dashed red line in A: single multi-whisker stimulus, red bar in B: 4 Hz multi-whisker stimulation. Grey shades indicate + SEM. Representative recording traces from 3 P7 animals are displayed.

Bottom Line: In the mature CNS it is well accepted that cortical sensory processing results in a rise in regional cerebral blood flow (rCBF).In contrast at P30, MUA remains stable during repetitive stimulation and is associated with an increase in rCBF.Further we characterize in both age groups the responses in NVC to single sensory stimuli.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology, University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.

ABSTRACT
Neurovascular coupling (NVC) in the adult central nervous system (CNS) is a mechanism that provides regions of the brain with more oxygen and glucose upon increased levels of neural activation. Hemodynamic changes that go along with neural activation evoke a blood oxygen level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) that can be used to study brain activity non-invasively. A correct correlation of the BOLD signal to neural activity is pivotal to understand this signal in neuronal development, health and disease. However, the function of NVC during development is largely unknown. The rodent whisker-to-barrel cortex is an experimentally well established model to study neurovascular interdependences. Using extracellular multi-electrode recordings and laser-Doppler-flowmetry (LDF) we show in the murine barrel cortex of postnatal day 7 (P7) and P30 mice in vivo that NVC undergoes a physiological shift during the first month of life. In the mature CNS it is well accepted that cortical sensory processing results in a rise in regional cerebral blood flow (rCBF). We show in P7 animals that rCBF decreases during prolonged multi-whisker stimulation and goes along with multi unit activity (MUA) fatigue. In contrast at P30, MUA remains stable during repetitive stimulation and is associated with an increase in rCBF. Further we characterize in both age groups the responses in NVC to single sensory stimuli. We suggest that the observed shift in NVC is an important process in cortical development that may be of high relevance for the correct interpretation of brain activity e.g. in fMRI studies of the immature central nervous system (CNS).

Show MeSH
Related in: MedlinePlus