Serotonergic innervation and serotonin receptor expression of NPY-producing neurons in the rat lateral and basolateral amygdaloid nuclei

Bonn, M.; Schmitt, Angelika; Lesch, Klaus‐Peter; Bockstaele, E. J. Van; Asan, Esther

doi:10.1007/s00429-012-0406-5

Cited by 58 publications

(54 citation statements)

References 92 publications

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“…In rats the amygdala receives dense and topographically organized serotonergic inputs from the raphe nucleus, with the BLA showing the highest density of 5-HT terminal innervation (Vertes et al, 1999, Muller et al, 2007, Bonn et al, 2013, Linley et al, 2017). The amygdala also shows moderate to high levels of ligand binding for multiple 5-HT receptor subtypes, including 5-HT 1A, 1B, 2A, 2C,3 and 5-HT 7 receptors (Gustafson et al, 1996, Saha et al, 2010, Bombardi, 2011, Bocchio et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, in this study application of 8-OH DPAT induced a slight yet non-significant increase of amplitude of eEPSCs. This effect may be due to an indirect activation of 5-HT 1A receptors located on NPY-expressing GABAergic interneurons (Bonn et al, 2013). Activation of 5-HT 1A receptors could in turn hyperpolarize GABA interneurons and lead to disinhibition of glutamate release.…”

Section: Discussionmentioning

confidence: 99%

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Serotonin gating of cortical and thalamic glutamate inputs onto principal neurons of the basolateral amygdala

2017

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The basolateral amygdala (BLA) is a key site for crossmodal association of sensory stimuli and an important relay in the neural circuitry of emotion. Indeed, the BLA receives substantial glutamatergic inputs from multiple brain regions including the prefrontal cortex and thalamic nuclei. Modulation of glutamatergic transmission in the BLA regulates stress- and anxiety-related behaviors. Serotonin (5-HT) also plays an important role in regulating stress-related behavior through activation of both pre- and postsynaptic 5-HT receptors. Multiple 5-HT receptors are expressed in the BLA, where 5-HT has been reported to modulate glutamatergic transmission. However, the 5-HT receptor subtype mediating this effect is not yet clear. The aim of this study was to use patch-clamp recordings from BLA neurons in an ex vivo slice preparation to examine 1) the effect of 5-HT on extrinsic sensory inputs, and 2) to determine if any pathway specificity exists in 5-HT regulation of glutamatergic transmission. Two independent input pathways into the BLA were stimulated: the external capsule to mimic cortical input, and the internal capsule to mimic thalamic input. Bath application of 5-HT reversibly reduced the amplitude of evoked excitatory postsynaptic currents (eEPSCs) induced by stimulation of both pathways. The decrease was associated with an increase in the paired-pulse ratio and coefficient of variation of eEPSC amplitude, suggesting 5-HT acts presynaptically. Moreover, the effect of 5-HT in both pathways was mimicked by the selective 5-HT1B receptor agonist CP93129, but not by the 5-HT1A receptor agonist 8-OH DPAT. Similarly the effect of exogenous 5-HT was blocked by the 5-HT1B receptor antagonist GR55562, but not affected by the 5-HT1A receptor antagonist WAY 100635 or the 5-HT2 receptor antagonists pirenperone and MDL 100907. Together these data suggest 5-HT gates cortical and thalamic glutamatergic inputs into the BLA by activating presynaptic 5-HT1B receptors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Serotonin gating of cortical and thalamic glutamate inputs onto principal neurons of the basolateral amygdala

2017

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“…The extracellular serotonin levels in downstream DRN targets, like the basolateral amygdala (BLA), can remain elevated for at least an hour after learning is completed [14,15]. Although serotonin acts through several receptor subtypes in the BLA, the serotonin 2c receptor (5-HT2CR) is of interest because these receptors are heavily expressed in BLA neurons that regulate anxiety [16] and 5-HT2CR agonists promote anxiety in humans [17]. Furthermore, viral-mediated overexpression of 5-HT2CR in amygdala produces anxiogenic effects [18] while pharmacological blockade of amygdala 5-HT2CR prevents stress-induced anxiety-like behaviors [19].…”

Section: Introductionmentioning

confidence: 99%

Stress Enables Reinforcement-Elicited Serotonergic Consolidation of Fear Memory

Baratta

Kodandaramaiah

Monahan

et al. 2016

Biological Psychiatry

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Background Prior exposure to stress is a risk factor for developing post-traumatic stress disorder (PTSD) in response to trauma, yet the mechanisms by which this occurs are unclear. Using a rodent model of stress-based susceptibility to PTSD, we investigated the role of serotonin in this phenomenon. Methods Adult mice were exposed to repeated immobilization stress or handling, and the role of serotonin in subsequent fear learning was assessed using pharmacological manipulation and western blot detection of serotonin receptors, measurements of serotonin, high-speed optogenetic silencing, and behavior. Results Both dorsal raphe serotonergic activity during aversive reinforcement and amygdala serotonin 2c receptor (5-HT2CR) activity during memory consolidation are necessary for stress enhancement of fear memory, but neither process affects fear memory in unstressed mice. Additionally, prior stress increases amygdala sensitivity to serotonin by promoting surface expression of 5-HT2CR without affecting tissue levels of serotonin in the amygdala. We also show that the serotonin that drives stress enhancement of associative cued fear memory can arise from paired or unpaired footshock, an effect not predicted by theoretical models of associative learning. Conclusion Stress bolsters the consequences of aversive reinforcement, not by simply enhancing the neurobiological signals used to encode fear in unstressed animals, but rather by engaging distinct mechanistic pathways. These results reveal that predictions from classical associative learning models do not always hold for stressed animals, and suggest that 5-HT2CR blockade may represent a promising therapeutic target for psychiatric disorders characterized by excessive fear responses such as that observed in PTSD.

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“…8 H ). Thus, pc-nNOS cells are hyperpolarized by 5-HT via 5-HT1A receptors, in line with the expression of 5-HT1A mRNA in NPY + BLA neurons (Bonn et al, 2013). …”

Section: Resultsmentioning

confidence: 70%

“…However, recent in situ hybridization data have shown that BLA NPY + cells, some of which are thought to be nNOS + (McDonald et al, 1993), can also express inhibitory 5-HT1A receptors (Bonn et al, 2013), suggesting that 5-HT could also hyperpolarize some GABAergic cells. Defining the diversity of 5-HT actions on BLA neuron types is crucial if we are to understand the cellular dynamics occurring in the BLA across different brain states.…”

Section: Introductionmentioning

confidence: 99%

Sleep and Serotonin Modulate Paracapsular Nitric Oxide Synthase Expressing Neurons of the Amygdala

Bocchio

Fisher

Ünal

et al. 2016

eNeuro

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Unraveling the roles of distinct neuron types is a fundamental challenge to understanding brain function in health and disease. In the amygdala, a brain structure regulating emotional behavior, the diversity of GABAergic neurons has been only partially explored. We report a novel population of GABAergic amygdala neurons expressing high levels of neuronal nitric oxide synthase (nNOS). These cells are predominantly localized along basolateral amygdala (BLA) boundaries. Performing ex vivo patch-clamp recordings from nNOS+ neurons in Nos1-CreER;Ai9 mice, we observed that nNOS+ neurons located along the external capsule display distinctive electrophysiological properties, axonal and dendritic arborization, and connectivity. Examining their c-Fos expression, we found that paracapsular nNOS+ neurons are activated during a period of undisturbed sleep following sleep deprivation, but not during sleep deprivation. Consistently, we found that dorsal raphe serotonin [5-hydroxytryptamine (5-HT)] neurons, which are involved in sleep–wake regulation, innervate nNOS+ neurons. Bath application of 5-HT hyperpolarizes nNOS+ neurons via 5-HT1A receptors. This hyperpolarization produces a reduction in firing rate and, occasionally, a switch from tonic to burst firing mode, thereby contrasting with the classic depolarizing effect of 5-HT on BLA GABAergic cells reported so far. Thus, nNOS+ cells are a distinct cell type of the amygdala that controls the activity of downstream neurons in both amygdaloid and extra-amygdaloid regions in a vigilance state-dependent fashion. Given the strong links among mood, sleep deprivation, and 5-HT, the recruitment of paracapsular nNOS+ neurons following high sleep pressure may represent an important mechanism in emotional regulation.

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Serotonergic innervation and serotonin receptor expression of NPY-producing neurons in the rat lateral and basolateral amygdaloid nuclei

Cited by 58 publications

References 92 publications

Serotonin gating of cortical and thalamic glutamate inputs onto principal neurons of the basolateral amygdala

Serotonin gating of cortical and thalamic glutamate inputs onto principal neurons of the basolateral amygdala

Stress Enables Reinforcement-Elicited Serotonergic Consolidation of Fear Memory

Sleep and Serotonin Modulate Paracapsular Nitric Oxide Synthase Expressing Neurons of the Amygdala

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