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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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Minimal stimulation of the mossy fibers triggers CA3 sharp waves.A, Stimulation pulses (arrows) were delivered to the infragranular zone of the hilus to activate the mossy fibers arising from a small portion of the granule cell population. This reliably triggered a negative-going, complex response in the apical dendrites (str. radiatum) of field CA3b; the size and shape of this response closely resembled those of spontaneous SPWs. High-pass filtered trace (100–400 Hz; time-locked to upper trace) showed that both the evoked response and spontaneous SPWs were accompanied by high frequency activity, particularly on their ascending phases. B, As with SPWs, the complex potentials elicited by mossy fiber stimulation were positive in sign when recorded at the boundary between str. lucidum and str. pyramidale. Note that a small mossy fiber response (asterisk) precedes the positive wave. The downward arrow denotes the stimulation pulse. C, The frequency distribution for the peak amplitude of the evoked waves (EWs) illustrates the highly variable nature of the responses over the course of a recording session. Note the extensive overlap for the evoked and spontaneous wave distributions.
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pone-0007761-g009: Minimal stimulation of the mossy fibers triggers CA3 sharp waves.A, Stimulation pulses (arrows) were delivered to the infragranular zone of the hilus to activate the mossy fibers arising from a small portion of the granule cell population. This reliably triggered a negative-going, complex response in the apical dendrites (str. radiatum) of field CA3b; the size and shape of this response closely resembled those of spontaneous SPWs. High-pass filtered trace (100–400 Hz; time-locked to upper trace) showed that both the evoked response and spontaneous SPWs were accompanied by high frequency activity, particularly on their ascending phases. B, As with SPWs, the complex potentials elicited by mossy fiber stimulation were positive in sign when recorded at the boundary between str. lucidum and str. pyramidale. Note that a small mossy fiber response (asterisk) precedes the positive wave. The downward arrow denotes the stimulation pulse. C, The frequency distribution for the peak amplitude of the evoked waves (EWs) illustrates the highly variable nature of the responses over the course of a recording session. Note the extensive overlap for the evoked and spontaneous wave distributions.

Mentions: If co-occurrence of large, mossy fiber mEPSCs can trigger a SPW, then minimal activation of the projections should have a comparable effect. Prior work suggests that this is the case. Specifically, spontaneous discharges of a sub-population of granule cells (‘dentate spikes’) are routinely followed by a sharp wave in field CA3 [19]. Explicit tests of the point were made here by asking if stimulation of a small population of mossy fibers generates a CA3 population event with the characteristics of a SPW. Stimulation pulses (3/min) were delivered to the infragranular zone near the tip of the internal wing of the dentate gyrus (Fig. 2A). Use of this site restricts activation to the fibers emerging from a small percentage of the total granule cell population. Single pulses reliably triggered a single negative-going, complex wave in the str. radiatum of field CA3b with a 3–4 ms delay in each of four slices. The responses occurred in isolation without after-potentials and had no evident effect on spontaneous SPWs (Fig. 9A). They were accompanied by high frequency, (100–400 Hz) ripple-like activity that was particularly evident on the rising phase of the potential, as was also the case for SPWs (Fig. 9A, top trace). The laminar profile for the evoked waves – negative in the dendrites, positive in the cell body layer (Fig. 9B) – also closely resembled that for SPWs. Importantly, the amplitude of the evoked waves varied substantially and unpredictably across stimulation pulses. The frequency distributions of peak amplitudes for the evoked and spontaneous waves were comparable (Fig. 9C). Stimulation of the commissural-associational projections did not elicit responses of the type just described. The field potentials were larger, shorter in duration, and lacked the complexity of those evoked by mossy fiber pulses; moreover, they had constant amplitudes and were not accompanied by low voltage, high frequency activity.


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)

Minimal stimulation of the mossy fibers triggers CA3 sharp waves.A, Stimulation pulses (arrows) were delivered to the infragranular zone of the hilus to activate the mossy fibers arising from a small portion of the granule cell population. This reliably triggered a negative-going, complex response in the apical dendrites (str. radiatum) of field CA3b; the size and shape of this response closely resembled those of spontaneous SPWs. High-pass filtered trace (100–400 Hz; time-locked to upper trace) showed that both the evoked response and spontaneous SPWs were accompanied by high frequency activity, particularly on their ascending phases. B, As with SPWs, the complex potentials elicited by mossy fiber stimulation were positive in sign when recorded at the boundary between str. lucidum and str. pyramidale. Note that a small mossy fiber response (asterisk) precedes the positive wave. The downward arrow denotes the stimulation pulse. C, The frequency distribution for the peak amplitude of the evoked waves (EWs) illustrates the highly variable nature of the responses over the course of a recording session. Note the extensive overlap for the evoked and spontaneous wave distributions.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2770848&req=5

pone-0007761-g009: Minimal stimulation of the mossy fibers triggers CA3 sharp waves.A, Stimulation pulses (arrows) were delivered to the infragranular zone of the hilus to activate the mossy fibers arising from a small portion of the granule cell population. This reliably triggered a negative-going, complex response in the apical dendrites (str. radiatum) of field CA3b; the size and shape of this response closely resembled those of spontaneous SPWs. High-pass filtered trace (100–400 Hz; time-locked to upper trace) showed that both the evoked response and spontaneous SPWs were accompanied by high frequency activity, particularly on their ascending phases. B, As with SPWs, the complex potentials elicited by mossy fiber stimulation were positive in sign when recorded at the boundary between str. lucidum and str. pyramidale. Note that a small mossy fiber response (asterisk) precedes the positive wave. The downward arrow denotes the stimulation pulse. C, The frequency distribution for the peak amplitude of the evoked waves (EWs) illustrates the highly variable nature of the responses over the course of a recording session. Note the extensive overlap for the evoked and spontaneous wave distributions.
Mentions: If co-occurrence of large, mossy fiber mEPSCs can trigger a SPW, then minimal activation of the projections should have a comparable effect. Prior work suggests that this is the case. Specifically, spontaneous discharges of a sub-population of granule cells (‘dentate spikes’) are routinely followed by a sharp wave in field CA3 [19]. Explicit tests of the point were made here by asking if stimulation of a small population of mossy fibers generates a CA3 population event with the characteristics of a SPW. Stimulation pulses (3/min) were delivered to the infragranular zone near the tip of the internal wing of the dentate gyrus (Fig. 2A). Use of this site restricts activation to the fibers emerging from a small percentage of the total granule cell population. Single pulses reliably triggered a single negative-going, complex wave in the str. radiatum of field CA3b with a 3–4 ms delay in each of four slices. The responses occurred in isolation without after-potentials and had no evident effect on spontaneous SPWs (Fig. 9A). They were accompanied by high frequency, (100–400 Hz) ripple-like activity that was particularly evident on the rising phase of the potential, as was also the case for SPWs (Fig. 9A, top trace). The laminar profile for the evoked waves – negative in the dendrites, positive in the cell body layer (Fig. 9B) – also closely resembled that for SPWs. Importantly, the amplitude of the evoked waves varied substantially and unpredictably across stimulation pulses. The frequency distributions of peak amplitudes for the evoked and spontaneous waves were comparable (Fig. 9C). Stimulation of the commissural-associational projections did not elicit responses of the type just described. The field potentials were larger, shorter in duration, and lacked the complexity of those evoked by mossy fiber pulses; moreover, they had constant amplitudes and were not accompanied by low voltage, high frequency activity.

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