Median Raphe Stimulation Disrupts Hippocampal Theta Via Rapid Inhibition and State-Dependent Phase Reset of Theta-Related Neural Circuitry

Jackson, Jesse; Dickson, Clayton T.; Bland, Brian H.

doi:10.1152/jn.00065.2008

Cited by 48 publications

(46 citation statements)

References 61 publications

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“…37,38 Thus, the serotonergic neurons may not have been able to follow the 24 Hz stimulation during an entire 5-min train. Low-frequency MR stimulation (0.5 Hz) but not high frequency (100 Hz) reportedly causes a statedependent reset of phase of the theta rhythm, 47 which is thought to increase stimulus-processing in hippocampal networks. In cats, the firing rates of serotonergic raphe neurons are directly correlated with arousal, highest during waking, less during slowwave sleep, and least during paradoxical sleep.…”

Section: Physiologic Cellular and Molecular Repair Mechanismsmentioning

confidence: 99%

Midbrain Raphe Stimulation Improves Behavioral and Anatomical Recovery from Fluid-Percussion Brain Injury

Gonzalez

Blaya

Alonso

et al. 2013

Journal of Neurotrauma

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The midbrain median raphe (MR) and dorsal raphe (DR) nuclei were tested for their capacity to regulate recovery from traumatic brain injury (TBI). An implanted, wireless self-powered stimulator delivered intermittent 8-Hz pulse trains for 7 days to the rat's MR or DR, beginning 4-6 h after a moderate parasagittal (right) fluid-percussion injury. MR stimulation was also examined with a higher frequency (24 Hz) or a delayed start (7 days after injury). Controls had sham injuries, inactive stimulators, or both. The stimulation caused no apparent acute responses or adverse long-term changes. In watermaze trials conducted 5 weeks post-injury, early 8-Hz MR and DR stimulation restored the rate of acquisition of reference memory for a hidden platform of fixed location. Short-term spatial working memory, for a variably located hidden platform, was restored only by early 8-Hz MR stimulation. All stimulation protocols reversed injury-induced asymmetry of spontaneous forelimb reaching movements tested 6 weeks post-injury. Post-mortem histological measurement at 8 weeks post-injury revealed volume losses in parietal-occipital cortex and decussating white matter (corpus callosum plus external capsule), but not hippocampus. The cortical losses were significantly reversed by early 8-Hz MR and DR stimulation, the white matter losses by all forms of MR stimulation. The generally most effective protocol, 8-Hz MR stimulation, was tested 3 days post-injury for its acute effect on forebrain cyclic adenosine monophosphate (cAMP), a key trophic signaling molecule. This procedure reversed injury-induced declines of cAMP levels in both cortex and hippocampus. In conclusion, midbrain raphe nuclei can enduringly enhance recovery from early disseminated TBI, possibly in part through increased signaling by cAMP in efferent targets. A neurosurgical treatment for TBI using interim electrical stimulation in raphe repair centers is suggested.

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Section: Physiologic Cellular and Molecular Repair Mechanismsmentioning

confidence: 99%

Midbrain Raphe Stimulation Improves Behavioral and Anatomical Recovery from Fluid-Percussion Brain Injury

Gonzalez

Blaya

Alonso

et al. 2013

Journal of Neurotrauma

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“…2), another function of these neurons may be to promote the onset of SIA epochs during SW sleep. Although the neural mechanisms responsible for generating the transient arousal state SIA are largely unknown (Jackson et al 2008;Jarosiewicz et al 2002), it has been shown that the cholinergic system plays an important role: knockout mice without the ␤2-subunit of nicotinic receptors showed decreased frequency of SIA occurrence (Lena et al 2004). This finding not only supports our proposal that the specific neuronal population we identified is likely cholinergic neurons but also suggests that MSvDB cholinergic neurons may be a crucial component of the SIA generation mechanism.…”

Section: New Insights On the Function Of Msvdb Pro-arousal Slow-firinmentioning

confidence: 99%

A distinctive subpopulation of medial septal slow-firing neurons promote hippocampal activation and theta oscillations

Zhang

Lin

Nicolelis

2011

Journal of Neurophysiology

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Although many previous studies have focused on understanding how MSVDB neurons fire rhythmic bursts to pace hippocampal theta oscillations, a significant portion of MSVDB neurons are slow-firing and thus do not pace theta oscillations. The function of these MSVDB neurons, especially their role in modulating hippocampal activity, remains unknown. We recorded MSVDB neuronal ensembles in behaving rats, and identified a distinct physiologically homogeneous subpopulation of slow-firing neurons (overall firing Ͻ4 Hz) that shared three features: 1) much higher firing rate during rapid eye movement sleep than during slow-wave (SW) sleep; 2) temporary activation associated with transient arousals during SW sleep; 3) brief responses (latency 15ϳ30 ms) to auditory stimuli. Analysis of the fine temporal relationship of their spiking and theta oscillations showed that unlike the theta-pacing neurons, the firing of these "pro-arousal" neurons follows theta oscillations. However, their activity precedes short-term increases in hippocampal oscillation power in the theta and gamma range lasting for a few seconds. Together, these results suggest that these pro-arousal slow-firing MSvDB neurons may function collectively to promote hippocampal activation. medial septum; small-amplitude irregular activity, auditory response; theta oscillations; cholinergic THE MEDIAL SEPTUM-VERTICAL LIMB of the diagonal band of Broca (MSvDB) heavily innervates the hippocampus through cholinergic, GABAergic, and glutamatergic projections (Gritti et al. 2006;Kiss et al. 1990;Kohler et al. 1984;Lewis et al. 1967). These projections are essential for normal hippocampal functions. Lesion or inactivation of MSvDB recapitulates the memory deficit resulting from hippocampal lesions and eliminates hippocampal theta oscillations (Gray and McNaughton 1983;Green and Arduini 1954;Mahut 1972;Mizumori et al. 1990;Winson 1978).To achieve a mechanistic understanding of the critical role of MSvDB in hippocampal functioning, it is essential to elucidate how the neuronal activity in MSvDB modulates hippocampal activity, in particular its dynamic interactions on fine temporal scales. Indeed, this issue has been studied extensively at the electrophysiological level over the last few decades. Those studies have largely focused on the fast-firing, rhythmic-bursting MSvDB neurons and have demonstrated that these cells are the pacemaker of hippocampal theta oscillations (Ford et al. 1989;Hangya et al. 2009;Morales et al. 1971;Petsche et al. 1962).However, in parallel with their heterogeneity in terms of neurotransmitters, the physiological properties of MSvDB neurons are similarly diverse. In addition to the extensively studied fast-firing, rhythmic-bursting neurons, many MSvDB neurons are nonetheless slow-firing and do not fire theta-range rhythmic bursts (Ford et al. 1989;Gaztelu and Buno 1982;Stewart and Fox 1989). As such, these latter cells are unlikely candidates to participate in pacing theta oscillations. The function of these slow-firing neurons remains unknown, in ...

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“…Although the exact targets of MRR are not known in every innervated brain area, MRR projection seems to be very specific in the HIPP and MS. In the HIPP of the rat, MRR establishes synaptic contacts with the somata or proximal dendrites of different types of interneurons, except parvalbumin-positive cells (Freund et al 1990; Acsády et al 1993; Papp et al 1999; Somogyi et al 2004; Varga et al 2009), and MRR provides a complex modulation of the hippocampal network activity (Assaf and Miller 1978; Vertes and Kocsis 1997; Jackson et al 2008). In the MS and diagonal band of Broca of the rat, MRR fibers give perisomatic and per-idendritic baskets onto parvalbumin and calbindin-positive GABAergic cells, specifically (Leranth and Vertes 1999; Aznar et al 2004).…”

Section: Introductionmentioning

confidence: 99%

The ascending median raphe projections are mainly glutamatergic in the mouse forebrain

et al. 2014

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The median raphe region (MRR) is thought to be serotonergic and plays an important role in the regulation of many cognitive functions. In the hippocampus (HIPP), the MRR exerts a fast excitatory control, partially through glutamatergic transmission, on a subpopulation of GABAergic interneurons that are key regulators of local network activity. However, not all receptors of this connection in the HIPP and in synapses established by MRR in other brain areas are known. Using combined anterograde tracing and immunogold methods, we show that the GluN2A subunit of the NMDA receptor is present in the synapses established by MRR not only in the HIPP, but also in the medial septum (MS) and in the medial prefrontal cortex (mPFC) of the mouse. We estimated similar amounts of NMDA receptors in these synapses established by the MRR and in local adjacent excitatory synapses. Using retrograde tracing and confocal laser scanning microscopy, we found that the majority of the projecting cells of the mouse MRR contain the vesicular glutamate transporter type 3 (vGluT3). Furthermore, using double retrograde tracing, we found that single cells of the MRR can innervate the HIPP and mPFC or the MS and mPFC simultaneously, and these double-projecting cells are also predominantly vGluT3-positive. Our results indicate that the majority of the output of the MRR is glutamatergic and acts through NMDA receptor-containing synapses. This suggests that key forebrain areas receive precisely targeted excitatory input from the MRR, which is able to synchronously modify activity in those regions via individual MRR cells with dual projections.

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Median Raphe Stimulation Disrupts Hippocampal Theta Via Rapid Inhibition and State-Dependent Phase Reset of Theta-Related Neural Circuitry

Cited by 48 publications

References 61 publications

Midbrain Raphe Stimulation Improves Behavioral and Anatomical Recovery from Fluid-Percussion Brain Injury

Midbrain Raphe Stimulation Improves Behavioral and Anatomical Recovery from Fluid-Percussion Brain Injury

A distinctive subpopulation of medial septal slow-firing neurons promote hippocampal activation and theta oscillations

The ascending median raphe projections are mainly glutamatergic in the mouse forebrain

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