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Pedunculopontine Nucleus Gamma Band Activity-Preconscious Awareness, Waking, and REM Sleep.

Urbano FJ, D'Onofrio SM, Luster BR, Beck PB, Hyde JR, Bisagno V, Garcia-Rill E - Front Neurol (2014)

Bottom Line: Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions.That is, the RAS may play an early permissive role in volition.These results provide novel information on the mechanisms controlling high-frequency activity related to waking and REM sleep by elements of the RAS.

View Article: PubMed Central - PubMed

Affiliation: IFIBYNE & ININFA-CONICET, University of Buenos Aires , Buenos Aires , Argentina.

ABSTRACT
The pedunculopontine nucleus (PPN) is a major component of the reticular activating system (RAS) that regulates waking and REM sleep, states of high-frequency EEG activity. Recently, we described the presence of high threshold, voltage-dependent N- and P/Q-type calcium channels in RAS nuclei that subserve gamma band oscillations in the mesopontine PPN, intralaminar parafascicular nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD). Cortical gamma band activity participates in sensory perception, problem solving, and memory. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions. That is, the RAS may play an early permissive role in volition. Our latest results suggest that (1) the manifestation of gamma band activity during waking may employ a separate intracellular pathway compared to that during REM sleep, (2) neuronal calcium sensor (NCS-1) protein, which is over expressed in schizophrenia and bipolar disorder, modulates gamma band oscillations in the PPN in a concentration-dependent manner, (3) leptin, which undergoes resistance in obesity resulting in sleep dysregulation, decreases sodium currents in PPN neurons, accounting for its normal attenuation of waking, and (4) following our discovery of electrical coupling in the RAS, we hypothesize that there are cell clusters within the PPN that may act in concert. These results provide novel information on the mechanisms controlling high-frequency activity related to waking and REM sleep by elements of the RAS.

No MeSH data available.


Related in: MedlinePlus

Effects of NCS-1 on PPN membrane oscillations. (A) Representative 1 s long current ramp-induced oscillations in a PPN neuron in SB + TTX extracellular solution and 1 μM NCS-1 in the recording pipette (left record, red). After 10 min of NCS-1 diffusing into the cell, the oscillatory activity increased slightly (middle record, green). However, after 25 min of NCS-1 diffusion both oscillation amplitude and frequency were increased (right record, blue). (B) Power spectrum of the records shown in (A) showing the increased amplitude and frequency of oscillations after 25 min exposure to 1 μM NCS-1. (C) The graph shows the mean peak amplitude in millivolt of oscillations in control cells recorded (black circles) that demonstrated no significant changes over time. Cells recorded using 0.5 μM NCS-1 also showed no significant changes over time (pink triangles). Cells recorded using 1 μM NCS-1 (blue stars) showed significant increases in mean peak oscillation amplitude at 20–30 min. Cells recoded using 5 μM NCS-1 (green downward triangles) showed no significant changes over time, but cells recorded using 10 μM NCS-1 (red squares) showed a significant increase in mean peak oscillation amplitude at 10 min, but not thereafter. *p < 0.05; **p < 0.01. These results suggest that NCS-1 at low concentrations potentiates beta/gamma oscillations in PPN neurons, but at high concentrations compatible with over expression it reduces or blocks high-frequency membrane oscillations (64, 79).
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Figure 2: Effects of NCS-1 on PPN membrane oscillations. (A) Representative 1 s long current ramp-induced oscillations in a PPN neuron in SB + TTX extracellular solution and 1 μM NCS-1 in the recording pipette (left record, red). After 10 min of NCS-1 diffusing into the cell, the oscillatory activity increased slightly (middle record, green). However, after 25 min of NCS-1 diffusion both oscillation amplitude and frequency were increased (right record, blue). (B) Power spectrum of the records shown in (A) showing the increased amplitude and frequency of oscillations after 25 min exposure to 1 μM NCS-1. (C) The graph shows the mean peak amplitude in millivolt of oscillations in control cells recorded (black circles) that demonstrated no significant changes over time. Cells recorded using 0.5 μM NCS-1 also showed no significant changes over time (pink triangles). Cells recorded using 1 μM NCS-1 (blue stars) showed significant increases in mean peak oscillation amplitude at 20–30 min. Cells recoded using 5 μM NCS-1 (green downward triangles) showed no significant changes over time, but cells recorded using 10 μM NCS-1 (red squares) showed a significant increase in mean peak oscillation amplitude at 10 min, but not thereafter. *p < 0.05; **p < 0.01. These results suggest that NCS-1 at low concentrations potentiates beta/gamma oscillations in PPN neurons, but at high concentrations compatible with over expression it reduces or blocks high-frequency membrane oscillations (64, 79).

Mentions: During recordings in PPN neurons (in the presence of SB + TTX), 1 μM NCS-1 increased the amplitude and frequency of ramp-induced oscillations within ~25 min of diffusion into the cell. Figure 2A is a representative example of ramp-induced membrane potential oscillations in a PPN neuron in the presence of SB + TTX. Shortly after patching, the ramp typically induced low amplitude oscillations in the beta/gamma range. Figure 2A green record shows that, after 10 min of recording, some increase in the oscillation frequency was present (also evident in Figure 2B as a green line in the power spectrum). After 25 min of recording, NCS-1 at 1 μM significantly increased the frequency of oscillations (blue record in Figure 2A and as the blue line in the power spectrum). The graph in Figure 2C shows that control cells manifested no significant changes in amplitude throughout the 30 min recording period. These values were not significantly different from each of the 0 min recordings using pipettes with NCS-1, so that the 0 min recordings are an accurate representation of control levels. When the pipette contained 0.5 μM NCS-1, no changes in amplitude were observed throughout the recording, suggesting that this concentration does not significantly affect oscillation amplitude. When using 1 μM NCS-1, however, the oscillation amplitude increased significantly by 20 min and thereafter, suggesting a gradual effect in tripling amplitude as the NCS-1 diffused into the cell. When using 5 μM NCS-1, there was a significant increase in amplitude at 5 min but not afterward. This effect was probably due to the low amplitude of the initial oscillations in this group of cells. There were no further changes observed, so that we conclude that the effect at 5 min was not consistent. When using 10 μM NCS-1, the oscillation amplitude immediately increased to four times the levels and gradually decreased until it was significantly reduced by 30 min. These effects suggest an immediate effect on amplitude by very high levels of NCS-1 that ultimately led to partial blockade. Based on these results, 1 μM NCS-1 seems to be the most critical concentration for promoting gamma oscillation modulation, although some effects were evident with 0.5 μM NCS-1 (64).


Pedunculopontine Nucleus Gamma Band Activity-Preconscious Awareness, Waking, and REM Sleep.

Urbano FJ, D'Onofrio SM, Luster BR, Beck PB, Hyde JR, Bisagno V, Garcia-Rill E - Front Neurol (2014)

Effects of NCS-1 on PPN membrane oscillations. (A) Representative 1 s long current ramp-induced oscillations in a PPN neuron in SB + TTX extracellular solution and 1 μM NCS-1 in the recording pipette (left record, red). After 10 min of NCS-1 diffusing into the cell, the oscillatory activity increased slightly (middle record, green). However, after 25 min of NCS-1 diffusion both oscillation amplitude and frequency were increased (right record, blue). (B) Power spectrum of the records shown in (A) showing the increased amplitude and frequency of oscillations after 25 min exposure to 1 μM NCS-1. (C) The graph shows the mean peak amplitude in millivolt of oscillations in control cells recorded (black circles) that demonstrated no significant changes over time. Cells recorded using 0.5 μM NCS-1 also showed no significant changes over time (pink triangles). Cells recorded using 1 μM NCS-1 (blue stars) showed significant increases in mean peak oscillation amplitude at 20–30 min. Cells recoded using 5 μM NCS-1 (green downward triangles) showed no significant changes over time, but cells recorded using 10 μM NCS-1 (red squares) showed a significant increase in mean peak oscillation amplitude at 10 min, but not thereafter. *p < 0.05; **p < 0.01. These results suggest that NCS-1 at low concentrations potentiates beta/gamma oscillations in PPN neurons, but at high concentrations compatible with over expression it reduces or blocks high-frequency membrane oscillations (64, 79).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4202729&req=5

Figure 2: Effects of NCS-1 on PPN membrane oscillations. (A) Representative 1 s long current ramp-induced oscillations in a PPN neuron in SB + TTX extracellular solution and 1 μM NCS-1 in the recording pipette (left record, red). After 10 min of NCS-1 diffusing into the cell, the oscillatory activity increased slightly (middle record, green). However, after 25 min of NCS-1 diffusion both oscillation amplitude and frequency were increased (right record, blue). (B) Power spectrum of the records shown in (A) showing the increased amplitude and frequency of oscillations after 25 min exposure to 1 μM NCS-1. (C) The graph shows the mean peak amplitude in millivolt of oscillations in control cells recorded (black circles) that demonstrated no significant changes over time. Cells recorded using 0.5 μM NCS-1 also showed no significant changes over time (pink triangles). Cells recorded using 1 μM NCS-1 (blue stars) showed significant increases in mean peak oscillation amplitude at 20–30 min. Cells recoded using 5 μM NCS-1 (green downward triangles) showed no significant changes over time, but cells recorded using 10 μM NCS-1 (red squares) showed a significant increase in mean peak oscillation amplitude at 10 min, but not thereafter. *p < 0.05; **p < 0.01. These results suggest that NCS-1 at low concentrations potentiates beta/gamma oscillations in PPN neurons, but at high concentrations compatible with over expression it reduces or blocks high-frequency membrane oscillations (64, 79).
Mentions: During recordings in PPN neurons (in the presence of SB + TTX), 1 μM NCS-1 increased the amplitude and frequency of ramp-induced oscillations within ~25 min of diffusion into the cell. Figure 2A is a representative example of ramp-induced membrane potential oscillations in a PPN neuron in the presence of SB + TTX. Shortly after patching, the ramp typically induced low amplitude oscillations in the beta/gamma range. Figure 2A green record shows that, after 10 min of recording, some increase in the oscillation frequency was present (also evident in Figure 2B as a green line in the power spectrum). After 25 min of recording, NCS-1 at 1 μM significantly increased the frequency of oscillations (blue record in Figure 2A and as the blue line in the power spectrum). The graph in Figure 2C shows that control cells manifested no significant changes in amplitude throughout the 30 min recording period. These values were not significantly different from each of the 0 min recordings using pipettes with NCS-1, so that the 0 min recordings are an accurate representation of control levels. When the pipette contained 0.5 μM NCS-1, no changes in amplitude were observed throughout the recording, suggesting that this concentration does not significantly affect oscillation amplitude. When using 1 μM NCS-1, however, the oscillation amplitude increased significantly by 20 min and thereafter, suggesting a gradual effect in tripling amplitude as the NCS-1 diffused into the cell. When using 5 μM NCS-1, there was a significant increase in amplitude at 5 min but not afterward. This effect was probably due to the low amplitude of the initial oscillations in this group of cells. There were no further changes observed, so that we conclude that the effect at 5 min was not consistent. When using 10 μM NCS-1, the oscillation amplitude immediately increased to four times the levels and gradually decreased until it was significantly reduced by 30 min. These effects suggest an immediate effect on amplitude by very high levels of NCS-1 that ultimately led to partial blockade. Based on these results, 1 μM NCS-1 seems to be the most critical concentration for promoting gamma oscillation modulation, although some effects were evident with 0.5 μM NCS-1 (64).

Bottom Line: Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions.That is, the RAS may play an early permissive role in volition.These results provide novel information on the mechanisms controlling high-frequency activity related to waking and REM sleep by elements of the RAS.

View Article: PubMed Central - PubMed

Affiliation: IFIBYNE & ININFA-CONICET, University of Buenos Aires , Buenos Aires , Argentina.

ABSTRACT
The pedunculopontine nucleus (PPN) is a major component of the reticular activating system (RAS) that regulates waking and REM sleep, states of high-frequency EEG activity. Recently, we described the presence of high threshold, voltage-dependent N- and P/Q-type calcium channels in RAS nuclei that subserve gamma band oscillations in the mesopontine PPN, intralaminar parafascicular nucleus (Pf), and pontine subcoeruleus nucleus dorsalis (SubCD). Cortical gamma band activity participates in sensory perception, problem solving, and memory. Rather than participating in the temporal binding of sensory events as in the cortex, gamma band activity in the RAS may participate in the processes of preconscious awareness, and provide the essential stream of information for the formulation of many of our actions. That is, the RAS may play an early permissive role in volition. Our latest results suggest that (1) the manifestation of gamma band activity during waking may employ a separate intracellular pathway compared to that during REM sleep, (2) neuronal calcium sensor (NCS-1) protein, which is over expressed in schizophrenia and bipolar disorder, modulates gamma band oscillations in the PPN in a concentration-dependent manner, (3) leptin, which undergoes resistance in obesity resulting in sleep dysregulation, decreases sodium currents in PPN neurons, accounting for its normal attenuation of waking, and (4) following our discovery of electrical coupling in the RAS, we hypothesize that there are cell clusters within the PPN that may act in concert. These results provide novel information on the mechanisms controlling high-frequency activity related to waking and REM sleep by elements of the RAS.

No MeSH data available.


Related in: MedlinePlus