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Suppression of piriform cortex activity in rat by corticotropin-releasing factor 1 and serotonin 2A/C receptors.

Narla C, Dunn HA, Ferguson SS, Poulter MO - Front Cell Neurosci (2015)

Bottom Line: Application of forskolin did not mimic CRFR1 activity but instead blocked it, while a protein kinase A antagonist had no effect.DOI had no effect when applied alone indicating that the prior activation of CRFR1 receptors was critical for DOI to show significant effects similar to CRF.These data show that CRF and 5-HT, acting through both CRFR1 and 5-HT2A/CRs, reduce the activation of the PC.

View Article: PubMed Central - PubMed

Affiliation: Molecular Medicine Research Group, Department of Physiology and Pharmacology, Robarts Research Institute, Faculty of Medicine, Schulich School of Medicine, University of Western Ontario London, ON, Canada.

ABSTRACT
The piriform cortex (PC) is richly innervated by corticotropin-releasing factor (CRF) and serotonin (5-HT) containing axons arising from central amygdala and Raphe nucleus. CRFR1 and 5-HT2A/2CRs have been shown to interact in manner where CRFR activation subsequently potentiates the activity of 5-HT2A/2CRs. The purpose of this study was to determine how the activation of CRFR1 and/or 5-HT2Rs modulates PC activity at both the circuit and cellular level. Voltage sensitive dye imaging showed that CRF acting through CRFR1 dampened activation of the Layer II of PC and interneurons of endopiriform nucleus. Application of the selective 5-HT2A/CR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) following CRFR1 activation potentiated this effect. Blocking the interaction between CRFR1 and 5-HT2R with a Tat-CRFR1-CT peptide abolished this potentiation. Application of forskolin did not mimic CRFR1 activity but instead blocked it, while a protein kinase A antagonist had no effect. However, activation and antagonism of protein kinase C (PKC) either mimicked or blocked CRF modulation, respectively. DOI had no effect when applied alone indicating that the prior activation of CRFR1 receptors was critical for DOI to show significant effects similar to CRF. Patch clamp recordings showed that both CRF and DOI reduced the synaptic responsiveness of Layer II pyramidal neurons. CRF had highly variable effects on interneurons within Layer III, both increasing and decreasing their excitability, but DOI had no effect on the excitability of this group of neurons. These data show that CRF and 5-HT, acting through both CRFR1 and 5-HT2A/CRs, reduce the activation of the PC. This modulation may be an important blunting mechanism of stressor behaviors mediated through the olfactory cortex.

No MeSH data available.


Related in: MedlinePlus

Activation of CRFR1 in PC reduced the activation of pyramidal cell layer (Layer II) and dorsal endopiriform nucleus (DEn) but attenuated the deactivation of interneuronal layer (Layer III). Representative images taken 1 s after the end of stimulation are shown in (A) before (left) and after the application of 100 nM CRF (middle 15 min) and after 20 min wash (right). In (B–D) we show quantification of CRFR1 effects over the range of stimulation frequencies used to activate the circuit. CRF was most effective on the 60 and 80 Hz stimulations. *p < 0.05.
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Figure 2: Activation of CRFR1 in PC reduced the activation of pyramidal cell layer (Layer II) and dorsal endopiriform nucleus (DEn) but attenuated the deactivation of interneuronal layer (Layer III). Representative images taken 1 s after the end of stimulation are shown in (A) before (left) and after the application of 100 nM CRF (middle 15 min) and after 20 min wash (right). In (B–D) we show quantification of CRFR1 effects over the range of stimulation frequencies used to activate the circuit. CRF was most effective on the 60 and 80 Hz stimulations. *p < 0.05.

Mentions: We wanted to investigate how CRF might modulate this response. This was done by comparing control input/output relationship (as shown in Figures 1B–D) to those obtained after ACSF containing 100 nM CRF was perfused over the slice. In Figure 2A, the left panel shows the control response (2 s after the stimulation) to an 80 Hz train. The middle panel shows the equivalent response after 15–20 min of 100 nM CRF application and the right most panel shows the response after CRF washout. CRF reduced the activity of pyramidal cell layer as evidenced by decreased signal (less red) in Layer II [F(1,9) = 6.58, p < 0.001, n = 9]. Similarly, the activity of neurons in DEn was also reduced which can be seen by decreased green/yellow/red scaling of the fluorescence signal. The decreased blue/violet color in Layer III represents decreased disinhibitory drive arising from the DEn neurons. In Figures 2B–D, we show the effect of CRF over the entire input/output relationships in the three areas tested. CRF reduced the activity of Layer II pyramidal cells and the cells in DEn as the curves shifted downward (Figures 2B,D). Application of CRF also reduced the inhibition of Layer III, thus shifting the curve upward. This CRF effect was reversible within 10 min (Figure 2C). We also found that the effects of CRF were most robust within γ-frequency range (40–80 Hz). There was no significant difference in fluorescence signals within θ to high β frequency range (5–20 Hz).


Suppression of piriform cortex activity in rat by corticotropin-releasing factor 1 and serotonin 2A/C receptors.

Narla C, Dunn HA, Ferguson SS, Poulter MO - Front Cell Neurosci (2015)

Activation of CRFR1 in PC reduced the activation of pyramidal cell layer (Layer II) and dorsal endopiriform nucleus (DEn) but attenuated the deactivation of interneuronal layer (Layer III). Representative images taken 1 s after the end of stimulation are shown in (A) before (left) and after the application of 100 nM CRF (middle 15 min) and after 20 min wash (right). In (B–D) we show quantification of CRFR1 effects over the range of stimulation frequencies used to activate the circuit. CRF was most effective on the 60 and 80 Hz stimulations. *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4446537&req=5

Figure 2: Activation of CRFR1 in PC reduced the activation of pyramidal cell layer (Layer II) and dorsal endopiriform nucleus (DEn) but attenuated the deactivation of interneuronal layer (Layer III). Representative images taken 1 s after the end of stimulation are shown in (A) before (left) and after the application of 100 nM CRF (middle 15 min) and after 20 min wash (right). In (B–D) we show quantification of CRFR1 effects over the range of stimulation frequencies used to activate the circuit. CRF was most effective on the 60 and 80 Hz stimulations. *p < 0.05.
Mentions: We wanted to investigate how CRF might modulate this response. This was done by comparing control input/output relationship (as shown in Figures 1B–D) to those obtained after ACSF containing 100 nM CRF was perfused over the slice. In Figure 2A, the left panel shows the control response (2 s after the stimulation) to an 80 Hz train. The middle panel shows the equivalent response after 15–20 min of 100 nM CRF application and the right most panel shows the response after CRF washout. CRF reduced the activity of pyramidal cell layer as evidenced by decreased signal (less red) in Layer II [F(1,9) = 6.58, p < 0.001, n = 9]. Similarly, the activity of neurons in DEn was also reduced which can be seen by decreased green/yellow/red scaling of the fluorescence signal. The decreased blue/violet color in Layer III represents decreased disinhibitory drive arising from the DEn neurons. In Figures 2B–D, we show the effect of CRF over the entire input/output relationships in the three areas tested. CRF reduced the activity of Layer II pyramidal cells and the cells in DEn as the curves shifted downward (Figures 2B,D). Application of CRF also reduced the inhibition of Layer III, thus shifting the curve upward. This CRF effect was reversible within 10 min (Figure 2C). We also found that the effects of CRF were most robust within γ-frequency range (40–80 Hz). There was no significant difference in fluorescence signals within θ to high β frequency range (5–20 Hz).

Bottom Line: Application of forskolin did not mimic CRFR1 activity but instead blocked it, while a protein kinase A antagonist had no effect.DOI had no effect when applied alone indicating that the prior activation of CRFR1 receptors was critical for DOI to show significant effects similar to CRF.These data show that CRF and 5-HT, acting through both CRFR1 and 5-HT2A/CRs, reduce the activation of the PC.

View Article: PubMed Central - PubMed

Affiliation: Molecular Medicine Research Group, Department of Physiology and Pharmacology, Robarts Research Institute, Faculty of Medicine, Schulich School of Medicine, University of Western Ontario London, ON, Canada.

ABSTRACT
The piriform cortex (PC) is richly innervated by corticotropin-releasing factor (CRF) and serotonin (5-HT) containing axons arising from central amygdala and Raphe nucleus. CRFR1 and 5-HT2A/2CRs have been shown to interact in manner where CRFR activation subsequently potentiates the activity of 5-HT2A/2CRs. The purpose of this study was to determine how the activation of CRFR1 and/or 5-HT2Rs modulates PC activity at both the circuit and cellular level. Voltage sensitive dye imaging showed that CRF acting through CRFR1 dampened activation of the Layer II of PC and interneurons of endopiriform nucleus. Application of the selective 5-HT2A/CR agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) following CRFR1 activation potentiated this effect. Blocking the interaction between CRFR1 and 5-HT2R with a Tat-CRFR1-CT peptide abolished this potentiation. Application of forskolin did not mimic CRFR1 activity but instead blocked it, while a protein kinase A antagonist had no effect. However, activation and antagonism of protein kinase C (PKC) either mimicked or blocked CRF modulation, respectively. DOI had no effect when applied alone indicating that the prior activation of CRFR1 receptors was critical for DOI to show significant effects similar to CRF. Patch clamp recordings showed that both CRF and DOI reduced the synaptic responsiveness of Layer II pyramidal neurons. CRF had highly variable effects on interneurons within Layer III, both increasing and decreasing their excitability, but DOI had no effect on the excitability of this group of neurons. These data show that CRF and 5-HT, acting through both CRFR1 and 5-HT2A/CRs, reduce the activation of the PC. This modulation may be an important blunting mechanism of stressor behaviors mediated through the olfactory cortex.

No MeSH data available.


Related in: MedlinePlus