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Origins of an intrinsic hippocampal EEG pattern.

Rex CS, Colgin LL, Jia Y, Casale M, Yanagihara TK, Debenedetti M, Gall CM, Kramar EA, Lynch G - PLoS ONE (2009)

Bottom Line: Antagonists of GABA-B mediated IPSCs also had little effect on incidence.It appears from these results that the spacing of SPWs is not dictated by slow potentials.Together, these results indicate that constitutive release from the mossy fiber terminal boutons regulates the incidence of SPWs and their contribution to information processing in hippocampus.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA, USA.

ABSTRACT
Sharp waves (SPWs) are irregular waves that originate in field CA3 and spread throughout the hippocampus when animals are alert but immobile or as a component of the sleep EEG. The work described here used rat hippocampal slices to investigate the factors that initiate SPWs and govern their frequency. Acute transection of the mossy fibers reduced the amplitude but not the frequency of SPWs, suggesting that activity in the dentate gyrus may enhance, but is not essential for, the CA3 waves. However, selective destruction of the granule cells and mossy fibers by in vivo colchicine injections profoundly depressed SPW frequency. Reducing mossy fiber release with an mGluR2 receptor agonist or enhancing it with forskolin respectively depressed or increased the incidence of SPWs. Collectively, these results indicate that SPWs can be triggered by constitutive release from the mossy fibers. The waves were not followed by large after-hyperpolarizing potentials and their frequency was not strongly affected by blockers of various slow potassium channels. Antagonists of GABA-B mediated IPSCs also had little effect on incidence. It appears from these results that the spacing of SPWs is not dictated by slow potentials. However, modeling work suggests that the frequency and variance of large mEPSCs from the mossy boutons can account for the temporal distribution of the waves. Together, these results indicate that constitutive release from the mossy fiber terminal boutons regulates the incidence of SPWs and their contribution to information processing in hippocampus.

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Effects of manipulating after-hyperpolarizing potentials (AHPs) on SPWs.A, ZD7288 (10 µM), an antagonist of I(h), reduces the AHP (arrow) found immediately after the composite EPSC produced by a brief burst of stimulation pulses, but has little effect on the later component of the AHP in CA3 neurons. Experiment was repeated in 3 cells from 3 slices. (i) SPWs recorded 10 minutes before and (ii) 10 minutes after the infusion of 10 µM ZD7288. Note the presence of a single small potential following each SPW under the latter conditions. (iii) Enlargement of example trace from (ii) indicates that the after-discharges have a similar waveform to SPWs. (iv) Power of the EEG spectrum (% baseline [bl]) in the SPW frequency range is unaffected by ZD7288 (n = 4 slices). B, Apamin (100 nM, 20 min), an inhibitor of SK channels, does not affect the composite EPSC elicited by a brief burst of afferent stimulation (left panel). Effect representative of 3 cells tested. Frequency and size of SPWs collected before (i) and during (ii) 100 nM apamin infusion are comparable. Records were collected from the apical dendrites of field CA3 and illustrate the reversed polarity associated with a local dipole. C, CGP55845 (50 µM, 20 min), an antagonist of GABA-B receptors, reduces the AHP elicited by an intense burst of afferent stimulation (left panel). Effect representative of 4 cells tested. SPWs observed 10 min prior to (i) and during (ii) 50 µM CGP55845 infusion did not show detectable differences in frequency or shape. (iii) The GABA-B antagonist produced a small depression of SPW amplitude (*p<0.05, paired t-test; n = 3) but did not reliably increase the frequency (p>0.3) of the waves. (BL:baseline; WO: washout).
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pone-0007761-g007: Effects of manipulating after-hyperpolarizing potentials (AHPs) on SPWs.A, ZD7288 (10 µM), an antagonist of I(h), reduces the AHP (arrow) found immediately after the composite EPSC produced by a brief burst of stimulation pulses, but has little effect on the later component of the AHP in CA3 neurons. Experiment was repeated in 3 cells from 3 slices. (i) SPWs recorded 10 minutes before and (ii) 10 minutes after the infusion of 10 µM ZD7288. Note the presence of a single small potential following each SPW under the latter conditions. (iii) Enlargement of example trace from (ii) indicates that the after-discharges have a similar waveform to SPWs. (iv) Power of the EEG spectrum (% baseline [bl]) in the SPW frequency range is unaffected by ZD7288 (n = 4 slices). B, Apamin (100 nM, 20 min), an inhibitor of SK channels, does not affect the composite EPSC elicited by a brief burst of afferent stimulation (left panel). Effect representative of 3 cells tested. Frequency and size of SPWs collected before (i) and during (ii) 100 nM apamin infusion are comparable. Records were collected from the apical dendrites of field CA3 and illustrate the reversed polarity associated with a local dipole. C, CGP55845 (50 µM, 20 min), an antagonist of GABA-B receptors, reduces the AHP elicited by an intense burst of afferent stimulation (left panel). Effect representative of 4 cells tested. SPWs observed 10 min prior to (i) and during (ii) 50 µM CGP55845 infusion did not show detectable differences in frequency or shape. (iii) The GABA-B antagonist produced a small depression of SPW amplitude (*p<0.05, paired t-test; n = 3) but did not reliably increase the frequency (p>0.3) of the waves. (BL:baseline; WO: washout).

Mentions: Recent work suggests that the I(h) (hyper-polarization activated cation current) is a principal source of the AHP that follows spike-free EPSCs elicited by stimulation of the Schaffer-collateral projections in hippocampal slices [42]. Consonant with this, the I(h) channel blocker ZD7288 at 10 µM [43], the half-maximal inhibitory concentration in CA1 [44], reduced the initial segment of the AHP recorded from CA3 neurons (recorded at −70 mV) that follows the composite EPSC elicited by a burst of afferent stimulation (Fig. 7A, arrow). ZD7288 hyperpolarized the pyramidal neurons by 5–7 mV, presumably because a significant number of I(h) channels are open under resting conditions. Despite its potent effects on mid-duration AHPs, ZD7288 did not change the mean frequency of the full-sized SPWs, although it did increase the likelihood that individual SPWs would be followed by 1–2 smaller waves (Fig. 7A, i–iv).


Origins of an intrinsic hippocampal EEG pattern.

Rex CS, Colgin LL, Jia Y, Casale M, Yanagihara TK, Debenedetti M, Gall CM, Kramar EA, Lynch G - PLoS ONE (2009)

Effects of manipulating after-hyperpolarizing potentials (AHPs) on SPWs.A, ZD7288 (10 µM), an antagonist of I(h), reduces the AHP (arrow) found immediately after the composite EPSC produced by a brief burst of stimulation pulses, but has little effect on the later component of the AHP in CA3 neurons. Experiment was repeated in 3 cells from 3 slices. (i) SPWs recorded 10 minutes before and (ii) 10 minutes after the infusion of 10 µM ZD7288. Note the presence of a single small potential following each SPW under the latter conditions. (iii) Enlargement of example trace from (ii) indicates that the after-discharges have a similar waveform to SPWs. (iv) Power of the EEG spectrum (% baseline [bl]) in the SPW frequency range is unaffected by ZD7288 (n = 4 slices). B, Apamin (100 nM, 20 min), an inhibitor of SK channels, does not affect the composite EPSC elicited by a brief burst of afferent stimulation (left panel). Effect representative of 3 cells tested. Frequency and size of SPWs collected before (i) and during (ii) 100 nM apamin infusion are comparable. Records were collected from the apical dendrites of field CA3 and illustrate the reversed polarity associated with a local dipole. C, CGP55845 (50 µM, 20 min), an antagonist of GABA-B receptors, reduces the AHP elicited by an intense burst of afferent stimulation (left panel). Effect representative of 4 cells tested. SPWs observed 10 min prior to (i) and during (ii) 50 µM CGP55845 infusion did not show detectable differences in frequency or shape. (iii) The GABA-B antagonist produced a small depression of SPW amplitude (*p<0.05, paired t-test; n = 3) but did not reliably increase the frequency (p>0.3) of the waves. (BL:baseline; WO: washout).
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2770848&req=5

pone-0007761-g007: Effects of manipulating after-hyperpolarizing potentials (AHPs) on SPWs.A, ZD7288 (10 µM), an antagonist of I(h), reduces the AHP (arrow) found immediately after the composite EPSC produced by a brief burst of stimulation pulses, but has little effect on the later component of the AHP in CA3 neurons. Experiment was repeated in 3 cells from 3 slices. (i) SPWs recorded 10 minutes before and (ii) 10 minutes after the infusion of 10 µM ZD7288. Note the presence of a single small potential following each SPW under the latter conditions. (iii) Enlargement of example trace from (ii) indicates that the after-discharges have a similar waveform to SPWs. (iv) Power of the EEG spectrum (% baseline [bl]) in the SPW frequency range is unaffected by ZD7288 (n = 4 slices). B, Apamin (100 nM, 20 min), an inhibitor of SK channels, does not affect the composite EPSC elicited by a brief burst of afferent stimulation (left panel). Effect representative of 3 cells tested. Frequency and size of SPWs collected before (i) and during (ii) 100 nM apamin infusion are comparable. Records were collected from the apical dendrites of field CA3 and illustrate the reversed polarity associated with a local dipole. C, CGP55845 (50 µM, 20 min), an antagonist of GABA-B receptors, reduces the AHP elicited by an intense burst of afferent stimulation (left panel). Effect representative of 4 cells tested. SPWs observed 10 min prior to (i) and during (ii) 50 µM CGP55845 infusion did not show detectable differences in frequency or shape. (iii) The GABA-B antagonist produced a small depression of SPW amplitude (*p<0.05, paired t-test; n = 3) but did not reliably increase the frequency (p>0.3) of the waves. (BL:baseline; WO: washout).
Mentions: Recent work suggests that the I(h) (hyper-polarization activated cation current) is a principal source of the AHP that follows spike-free EPSCs elicited by stimulation of the Schaffer-collateral projections in hippocampal slices [42]. Consonant with this, the I(h) channel blocker ZD7288 at 10 µM [43], the half-maximal inhibitory concentration in CA1 [44], reduced the initial segment of the AHP recorded from CA3 neurons (recorded at −70 mV) that follows the composite EPSC elicited by a burst of afferent stimulation (Fig. 7A, arrow). ZD7288 hyperpolarized the pyramidal neurons by 5–7 mV, presumably because a significant number of I(h) channels are open under resting conditions. Despite its potent effects on mid-duration AHPs, ZD7288 did not change the mean frequency of the full-sized SPWs, although it did increase the likelihood that individual SPWs would be followed by 1–2 smaller waves (Fig. 7A, i–iv).

Bottom Line: Antagonists of GABA-B mediated IPSCs also had little effect on incidence.It appears from these results that the spacing of SPWs is not dictated by slow potentials.Together, these results indicate that constitutive release from the mossy fiber terminal boutons regulates the incidence of SPWs and their contribution to information processing in hippocampus.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy & Neurobiology, University of California Irvine, Irvine, CA, USA.

ABSTRACT
Sharp waves (SPWs) are irregular waves that originate in field CA3 and spread throughout the hippocampus when animals are alert but immobile or as a component of the sleep EEG. The work described here used rat hippocampal slices to investigate the factors that initiate SPWs and govern their frequency. Acute transection of the mossy fibers reduced the amplitude but not the frequency of SPWs, suggesting that activity in the dentate gyrus may enhance, but is not essential for, the CA3 waves. However, selective destruction of the granule cells and mossy fibers by in vivo colchicine injections profoundly depressed SPW frequency. Reducing mossy fiber release with an mGluR2 receptor agonist or enhancing it with forskolin respectively depressed or increased the incidence of SPWs. Collectively, these results indicate that SPWs can be triggered by constitutive release from the mossy fibers. The waves were not followed by large after-hyperpolarizing potentials and their frequency was not strongly affected by blockers of various slow potassium channels. Antagonists of GABA-B mediated IPSCs also had little effect on incidence. It appears from these results that the spacing of SPWs is not dictated by slow potentials. However, modeling work suggests that the frequency and variance of large mEPSCs from the mossy boutons can account for the temporal distribution of the waves. Together, these results indicate that constitutive release from the mossy fiber terminal boutons regulates the incidence of SPWs and their contribution to information processing in hippocampus.

Show MeSH
Related in: MedlinePlus