α2‐Adrenoreceptor activation inhibits LTP and LTD in the basolateral amygdala: involvement of Gi/o‐protein‐mediated modulation of Ca2+‐channels and inwardly rectifying K+‐channels in LTD

deBock, Frederic; Kurz, Jörg; Azad, Shahnaz Christina; Parsons, Chris G.; Hapfelmeier, Gerhard; Zieglgänsberger, W.; Rammes, Gerhard

doi:10.1046/j.1460-9568.2003.02544.x

Cited by 77 publications

(67 citation statements)

References 56 publications

(74 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 C and F; n ϭ 6, t test, P ϭ 0.28). This observation is surprising because it has been demonstrated previously that NE, acting on specific adrenoreceptor subtypes, could either inhibit or facilitate glutamatergic synaptic transmission in lateral or basal nuclei of the amygdala (17)(18)(19)(20). In agreement with previous studies, we found that activation of ␤-adrenoreceptors by 10 M NE in the presence of the ␣ 2 -adrenoreceptor antagonist yohimbine (20 M) led to potentiation of the thalamo-amygdala EPSC to 149 Ϯ 10% of its initial value ( Fig.…”

Section: Resultssupporting

confidence: 89%

Norepinephrine enables the induction of associative long-term potentiation at thalamo-amygdala synapses

Tully

Tsvetkov

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

174

160

View full text Add to dashboard Cite

Emotional arousal, linked to a surge of norepinephrine (NE) in the amygdala, leads to creation of stronger and longer-lasting memories. However, little is known about the synaptic mechanisms of such modulatory NE influences. Long-term potentiation (LTP) in auditory inputs to the lateral nucleus of the amygdala was recently linked to the acquisition of fear memory. Therefore we explored whether LTP induction at thalamo-amygdala projections, conveying the acoustic conditioned stimulus information to the amygdala during fear conditioning, is under adrenergic control. Using wholecell recordings from amygdala slices, we show that NE suppresses GABAergic inhibition of projection neurons in the lateral amygdala and enables the induction of LTP at thalamo-amygdala synapses under conditions of intact GABAA receptor-mediated inhibition. Our data indicate that the NE effects on the efficacy of inhibition could result from a decrease in excitability of local circuit interneurons, without direct effects of NE on release machinery of the GABA-containing vesicles or the size of single-quanta postsynaptic GABAA receptor-mediated responses. Thus, adrenergic modulation of local interneurons may contribute to the formation of fear memory by gating LTP in the conditioned stimulus pathways.GABA ͉ synaptic plasticity M emory enhancements for emotionally charged events are thought to be associated with the release of norepinephrine in the amygdala (1, 2), which is also a key brain structure in another cognitive process, emotional learning (3). Strong emotional memories could be established through fear conditioning, a form of associative learning, which results from assigning of predictive properties to an initially neutral conditioned stimulus (CS) after its pairing with an aversive unconditioned stimulus during behavioral training (3-5). Previous studies provide evidence for the correlative link between long-term potentiation in the CS pathways conveying auditory information to the lateral amygdala (LA) and fear learning (6-10). A recent work has confirmed and extended these earlier findings by showing that synaptic enhancements at the cortico-amygdala synapses could be observed in slices from conditioned animals for at least 10 days after fear conditioning (11). The persistent facilitation of synaptic transmission in cortico-amygdala pathway is accompanied by occlusion of long-term potentiation (LTP) induced by electrical stimulation in slices (8). Although further studies will be needed to establish unequivocally the link between LTP and behavior, these findings indicate that behaviorally induced plasticity in the neural circuits of fear learning may use LTP mechanisms. Whereas the LA receives noradrenergic projections from the locus coeruleus (12), it remains unknown whether norepinephrine release in the amygdala, associated with the acquisition of fear memory, may contribute to fear behavior by affecting the mechanisms of synaptic plasticity in afferent inputs that deliver the CS information to the LA.During fear conditioning, a...

show abstract

Section: Resultssupporting

confidence: 89%

Norepinephrine enables the induction of associative long-term potentiation at thalamo-amygdala synapses

Tully

Tsvetkov

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

174

160

View full text Add to dashboard Cite

show abstract

“…There are two reports from the same group that tetanus stimulation of the LA in the mouse brain slices elicits modest LTP (1.2-to 1.4-fold increase to pre-tetanus) in the BLA (DeBock et al, 2003;Rammes et al, 2000). In our present study, however, we did not observe consistent BLA-LTP in wild-type mice.…”

Section: Ltp In the La-bla Synapsescontrasting

confidence: 90%

Heightened Amygdala Long-Term Potentiation in Neurotensin Receptor Type-1 Knockout Mice

Amano

Wada

Yamada

et al. 2008

Neuropsychopharmacol

View full text Add to dashboard Cite

Neurotensin receptor type-1 (Ntsr1) is the main receptor subtype that underlies neurotensin (NT)-mediated modulation of the dopamine (DA) system. Although NT and DA coexist in the basolateral nucleus of the amygdala (BLA), the function of Ntsr1 in the amygdala is not well characterized. In the present study, we utilized Ntsr1 knockout (Ntsr1-KO) mice to examine the role of Ntsr1 in the amygdala. In acute brain slices of Ntsr1-KO mice, synaptic currents elicited in BLA pyramidal neurons by electrical stimulation of the lateral nucleus of the amygdala (LA) were greatly potentiated by tetanic stimulation (BLA-long-term potentiation (LTP)). Such potentiation was not evident in pyramidal neurons of wild-type mice. In the presence of an antagonist of Ntsr1, SR48692, BLA-LTP was consistently observed in the neurons of wild-type mice, suggesting that both inherited deletion and acute pharmacological blockade of Ntsr1 induce BLA-LTP. BLA-LTP in Ntsr1-KO mice was impaired by sulpiride, a DA D 2 -like receptor antagonist. Conversely, quinpirole, a D 2 -like receptor agonist, induced pronounced BLA-LTP in wild-type mice, suggesting the upregulation of D 2 -like receptor activity in Ntsr1-KO mice. The ratio of NMDA receptor-mediated to non-NMDA receptor-mediated synaptic currents in Ntsr1-KO mouse BLA neurons was approximately double that measured in wild-type mouse neurons. Furthermore, quinpirole potentiated NMDA receptormediated synaptic currents in the BLA of wild-type mice. These results suggest that, without Ntsr1, synaptic responses from the LA to BLA pyramidal neurons undergo LTP in response to tetanus stimulation through facilitation of D 2 -like receptor-induced activation of NMDA receptors.

show abstract

“…To test for G i /G o -dependent actions of AgRP, slices were preincubated for at least 4 h in either pertussis toxin (PTX) (5 ug/ml) or 8,8Ј-[carbonylbis(imino-3,1-phenylene)]bis-(1,3,5-naphthalenetrisulfonic acid) (NF023) (10 uM) at 37°C as previously described Freissmuth et al, 1996;DeBock et al, 2003;Garic-Stankovic et al, 2005).…”

Section: Methodsmentioning

confidence: 99%

“…The G i/o -protein antagonists PTX and NF023 were used Freissmuth et al, 1996). Brain slices were preincubated in PTX or NF023 as described previously (DeBock et al, 2003;Garic-Stankovic et al, 2005) before using for whole-cell recording. AgRP (100 nM) failed to decrease the frequency of EPSCs significantly in either PTX-pretreated slices (84 Ϯ 6% of control; p Ͼ 0.05; ANOVA; n ϭ 6) or NF023-pretreated slices (94 Ϯ 12% of control; p Ͼ 0.05; ANOVA; n ϭ 7) (Fig.…”

Section: Agrp Inhibition In Vglut2 Neurons In Vmh Is G I/o -Protein Dmentioning

confidence: 99%

Agouti-Related Peptide and MC3/4 Receptor Agonists Both Inhibit Excitatory Hypothalamic Ventromedial Nucleus Neurons

Pol²

2008

J. Neurosci.

View full text Add to dashboard Cite

Anorexigenic melanocortins decrease food intake by activating MC3/MC4 receptors (MC3/4R); the prevailing view is that the orexigenic neuropeptide agouti-related peptide (AgRP) exerts the opposite action by acting as an antagonist at MC3/MC4 receptors. A total of 370 hypothalamic ventromedial nucleus (VMH) glutamatergic neurons was studied using whole-cell recording in hypothalamic slices from a novel mouse expressing green fluorescent protein (GFP) under control of the vesicular glutamate transporter 2 (vGluT2) promoter. Massive numbers of GFP-expressing VMH dendrites extended out of the core of the nucleus into the surrounding cell-poor shell. VMH dendrites received frequent appositions from AgRP-immunoreactive axons in the shell of the nucleus, but not the core, suggesting that AgRP may influence target VMH neurons. ␣-MSH, melanotan II (MTII), and selective MC3R or MC4R agonists were all inhibitory, reducing the spontaneous firing rate and hyperpolarizing vGluT2 neurons. The MC3/4R antagonist SHU9119 was excitatory. Unexpectedly, AgRP did not attenuate MTII actions on these neurons; instead, these two compounds showed an additive inhibitory effect. In the absence of synaptic activity, no hyperpolarization or change in input resistance was evoked by either MTII or AgRP, suggesting indirect actions. Consistent with this view, MTII increased the frequency of spontaneous and miniature IPSCs. In contrast, the mechanism of AgRP inhibition was dependent on presynaptic inhibition of EPSCs mediated by G i /G o -proteins, and was attenuated by pertussis toxin and NF023, inconsistent with mediation by G s -proteins associated with MC receptors. Together, our data suggest that the mechanism of AgRP actions on these excitatory VMH cells appears to be independent of the actions of melanocortins on MC receptors.

show abstract

α₂‐Adrenoreceptor activation inhibits LTP and LTD in the basolateral amygdala: involvement of G_i/o‐protein‐mediated modulation of Ca²⁺‐channels and inwardly rectifying K⁺‐channels in LTD

Cited by 77 publications

References 56 publications

Norepinephrine enables the induction of associative long-term potentiation at thalamo-amygdala synapses

Norepinephrine enables the induction of associative long-term potentiation at thalamo-amygdala synapses

Heightened Amygdala Long-Term Potentiation in Neurotensin Receptor Type-1 Knockout Mice

Agouti-Related Peptide and MC3/4 Receptor Agonists Both Inhibit Excitatory Hypothalamic Ventromedial Nucleus Neurons

Contact Info

Product

Resources

About