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

Szőnyi, András; Mayer, Márton I.; Cserép, Csaba; Takács, Virág T.; Watanabe, Masahiko; Freund, Tamás F.; Nyíri, Gábor

doi:10.1007/s00429-014-0935-1

Cited by 47 publications

(62 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MHb is connected to the MRN directly and indirectly via the IPN (Contestabile et al, 1987; Groenewegen et al, 1986; Herkenham and Nauta, 1979; Ogawa et al, 2014). The downstream connectivity of the MHb leading to a potential modulation of the MRN strongly suggests its role in regulating cognitive and emotional behaviors (Deakin, 2013; Herkenham and Nauta, 1979; Hsu et al, 2014; Ogawa et al, 2014; Szonyi et al, 2014; Varga et al, 2009). A recent study implicated the dMHb in the regulation of fear behavior (Yamaguchi et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Apart from a strong IPN output to the median raphe nucleus (MRN), recent data suggests that the MRN receives direct input from the MHb (Herkenham and Nauta, 1979; Ogawa et al, 2014). Therefore, the MHb could play a key role in an MRN-mediated modulation of other brain areas, particularly the hippocampus and the medial prefrontal cortex (Szonyi et al, 2014; Varga et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Development- and experience-dependent plasticity in the dorsomedial habenula

Koppensteiner

Galvin

2016

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

Of the two major subdivisions of the habenula, the medial and lateral nuclei, the medial habenula is the least understood in terms of synaptic transmission, intrinsic properties and plasticity. The medial habenula (MHb) is composed of glutamatergic neurons which receive the majority of their inputs from the septal region and project predominantly to the interpeduncular nucleus (IPN). To understand the synaptic transmission, we studied both glutamatergic and GABAergic synaptic transmission in the dorsal region of the medial habenula (dMHb). While glutamatergic transmission dominates during early development, an attenuation of glutamatergic transmission and an enhancement of GABAergic transmission occur during development leading into adulthood. Furthermore, as reported previously, GABAA receptor-mediated transmission is excitatory in the adult dMHb, which is consistent with the reduced expression of the K-Cl co-transporter KCC2. Given the potential role of the dMHb in aversive behaviors, we examined whether fear conditioning or exposure to foot shock affects excitability in dMHb neurons. We observed a suppression of the excitability of dMHb neurons in mice that either underwent fear conditioning or were exposed to foot shock. Furthermore, we observed a suppression of GABAergic but not glutamatergic transmission in the dMHb neurons following fear conditioning. These results suggest that aversive experience produces a suppression of the dMHb neuronal activity. Given that the medial habenula is upstream of the median raphe nucleus which is believed to be involved in the negative regulation of aversive memory, the suppression of dMHb neurons following an aversive experience might play a role in strengthening of aversive memories.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development- and experience-dependent plasticity in the dorsomedial habenula

Koppensteiner

Galvin

2016

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

show abstract

“…Previously, we extensively tested the rabbit anti-VGLUT3 antibody in experiments using VGLUT3 knock out animals (Szőnyi et al 2014). Immunostaining of VGLUT3 in raphe neurons was also tested by others (Mintz and Scott 2006; Shutoh et al 2008).…”

Section: Methodsmentioning

confidence: 99%

“…Serotonergic neurons desynchronize the hippocampal activity and disrupt rhythmic discharge of septal cholinergic and GABAergic neurons (Assaf and Miller 1978; Kinney et al 1996; Vertes and Kocsis 1997). VGLUT3 containing glutamatergic neurons suppress the hippocampal ripple activity and disrupt memory consolidation (Wang et al 2015), and both of these cells can innervate more forebrain areas simultaneously (Szőnyi et al 2014). Although serotonergic and glutamatergic neurons are frequently investigated, it is unknown how many of them possess both transmitters.…”

Section: Introductionmentioning

confidence: 99%

Cellular architecture and transmitter phenotypes of neurons of the mouse median raphe region

et al. 2016

Self Cite

View full text Add to dashboard Cite

The median raphe region (MRR, which consist of MR and paramedian raphe regions) plays a crucial role in regulating cortical as well as subcortical network activity and behavior, while its malfunctioning may lead to disorders, such as schizophrenia, major depression, or anxiety. Mouse MRR neurons are classically identified on the basis of their serotonin (5-HT), vesicular glutamate transporter type 3 (VGLUT3), and gamma-aminobutyric acid (GABA) contents; however, the exact cellular composition of MRR regarding transmitter phenotypes is still unknown. Using an unbiased stereological method, we found that in the MR, 8.5 % of the neurons were 5-HT, 26 % were VGLUT3, and 12.8 % were 5-HT and VGLUT3 positive; whereas 37.2 % of the neurons were GABAergic, and 14.4 % were triple negative. In the whole MRR, 2.1 % of the neurons were 5-HT, 7 % were VGLUT3, and 3.6 % were 5-HT and VGLUT3 positive; whereas 61 % of the neurons were GABAergic. Surprisingly, 25.4 % of the neurons were triple negative and were only positive for the neuronal marker NeuN. PET-1/ePET-Cre transgenic mouse lines are widely used to specifically manipulate only 5-HT containing neurons. Interestingly, however, using the ePET-Cre transgenic mice, we found that far more VGLUT3 positive cells expressed ePET than 5-HT positive cells, and about 38 % of the ePET cells contained only VGLUT3, while more than 30 % of 5-HT cells were ePET negative. These data should facilitate the reinterpretation of PET-1/ePET related data in the literature and the identification of the functional role of a putatively new type of triple-negative neuron in the MRR.

show abstract

“…Moreover, serotonergic nuclei also host glutamatergic mechanisms [6, 7], which are implicated in brain plasticity as well [8, 9]. In fact, earlier studies showed that the median raphe region (MRR) rather than the dorsal raphe (DRN) have a role in this process.…”

Section: Introductionmentioning

confidence: 99%

Median raphe region stimulation alone generates remote, but not recent fear memory traces

et al. 2017

Self Cite

View full text Add to dashboard Cite

The median raphe region (MRR) is believed to control the fear circuitry indirectly, by influencing the encoding and retrieval of fear memories by amygdala, hippocampus and prefrontal cortex. Here we show that in addition to this established role, MRR stimulation may alone elicit the emergence of remote but not recent fear memories. We substituted electric shocks with optic stimulation of MRR in C57BL/6N male mice in an optogenetic conditioning paradigm and found that stimulations produced agitation, but not fear, during the conditioning trial. Contextual fear, reflected by freezing was not present the next day, but appeared after a 7 days incubation. The optogenetic silencing of MRR during electric shocks ameliorated conditioned fear also seven, but not one day after conditioning. The optogenetic stimulation patterns (50Hz theta burst and 20Hz) used in our tests elicited serotonin release in vitro and lead to activation primarily in the periaqueductal gray examined by c-Fos immunohistochemistry. Earlier studies demonstrated that fear can be induced acutely by stimulation of several subcortical centers, which, however, do not generate persistent fear memories. Here we show that the MRR also elicits fear, but this develops slowly over time, likely by plastic changes induced by the area and its connections. These findings assign a specific role to the MRR in fear learning. Particularly, we suggest that this area is responsible for the durable sensitization of fear circuits towards aversive contexts, and by this, it contributes to the persistence of fear memories. This suggests the existence a bottom-up control of fear circuits by the MRR, which complements the top-down control exerted by the medial prefrontal cortex.

show abstract

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

Cited by 47 publications

References 51 publications

Development- and experience-dependent plasticity in the dorsomedial habenula

Development- and experience-dependent plasticity in the dorsomedial habenula

Cellular architecture and transmitter phenotypes of neurons of the mouse median raphe region

Median raphe region stimulation alone generates remote, but not recent fear memory traces

Contact Info

Product

Resources

About