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Intra-amygdala injections of NPS block fear-potentiated startle - PowerPoint PPT Presentation

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NPS Mediated Control of Fear Expression and Extinction: Role of Intercalated GABAergic Neurons in the Amygdala.

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NPS Mediated Control of Fear Expression and Extinction: Role of Intercalated GABAergic Neurons in the Amygdala

Kay Jungling, Thomas Seidenbecher, Ludmila Sosulina, Jorg Lesting, Susan Sangha, Stewart D. Clark, Naoe Okamura, Dee M. Duangdao, Yan-Ling Xu, Rainer K. Reinscheid, and Hans-Christian Pape

Intra amygdala injections of nps block fear potentiated startle
Intra-amygdala injections of NPS block fear-potentiated startle

  • fear ↓ effect of NPS independent of locomotor activity

  • Fear potentiated startle

    • Separate out NPS anxiolytic effect from locomotor effect

  • bi-lateral amygdala NPS injection

  • Fear potentiated startle protocol then motility boxes

Fig 2 startle

Effective Dose

Identification of a nps responsive circuitry shaping amygdala activity via the endopiriform nucleus
Identification of a startleNPS Responsive Circuitry Shaping Amygdala Activity via the Endopiriform Nucleus


  • NPS stimulates GABAergic input of BLA projection neurons

  • NPS effects in BLA interneurons

  • NPS stimulates glutamatergic input of BLA interneurons

  • NPS stimulates glutamatergic input of BLA projection neurons

Fig 5: startleEffects of mechanical circuit dissection

(B) Cuts detaching endopiriform nucleus from BLA eliminate NPS action upon sIPSCs in BLA projection neurons

(C, D) Only dissection in between EPN and BLA diminish (C) amplitude or (D) frequency ratio: NPS/control significantly

Fig 7: Behavioral effects of NPS startle

-NPS into EPN

.1 nmol NPS effective dose here

Endopiriform nucleus shapes bla activity response
Endopiriform Nucleus shapes BLA activity/response startle

  • NPS in EPN controls neural activity of BLA

  • NPS exerts direct action (mech) on EPN that ↑ Glu transmission

  • EPN required for NPS modulation of GABAA feedback & feedforward inhibition of BLA

  • Conditioned fear expression

    • NPS to EPN ↓ contextual (where) but NOT cued (what) fear memory in mice

Jungling intro
Jungling Intro startle

  • Injection of NPS into BLA – anxiolytic effect

    • acute reduction in general anxiety and

    • accelerated extinction of conditioned fear

    • injection of the NPS receptor antagonist SHA 68 exerted functionally opposing effects.

  • NPS ↑ glutamatergic synaptic transmission to intercalated GABAergic neurons of medial paracapsular cluster via a presynaptic effect

    • involving principal neurons in the LA

medial paracapsular cluster startle


Intro cont
Intro Cont. startle

  • NPSR’s densely expressed in the mouse BLA

    • at single-cell level, in LA principal neurons

    • Not in paracapsular GABAergic neurons

Methods startle

  • C57BL/6J mice, 8-12 wks old

  • Bilateral injections into BLA/LA

  • One animal per behavioral test/drug group

  • Open field, EPM, dark-light test, fear cond.

  • Amygdala coronal slices, whole-cell patch clamp

Figure 1 startle

Effects of NPS in the LA/BLA on generalized anxiety behavior in the open field and elevated plus maze

Fig 2 startle

Effects of NPS in the LA/BLA during retrieval and extinction of conditioned fear

Fig 3: startleTarget specific effect of NPS on evoked EPSCs

mpara neurons provide a feedforward inhibitory gate for signals between BLA and CeA

Fig 4: startleLack of NPS modulatory influence in LA Principle Neurons (PN) and LA local GABAergic interneurons (IN)

Fig 5: startleNPS reduces failure-rates of glutamatergic transmission to mpara IN

Fig 6: startlePresynaptic site of NPS modulation

Fig 7: startleNPS receptor expression in the amygdala

opt: optic tract

BLA: basolateral amygdaloid complex, anterior part

BMA: basomedial amygdaloid nucleus, anterior part

MeAV: medial amygdaloid nucleus, anteroventral part ACo: anterior cortical amygdaloid nucleus

ic: internal capsule

DI: dysgranular insular cortex

GI: granular insular cortex AIP: agranular insular cortex, posterior part

LaDL: lateral amygdaloid nucleus, dorsolateral part

DEn: dorsal endopiriform nucleus

Fig 8: startleNPS enforces feed forward inhibition on principal neurons in the central nucleus of the amygdala (CeA)

Take home
Take Home startle

  • Endogenous NPS has a dual function to acutely attenuate anxiety-like responses and later facilitate extinction of aversive memories

Thank you startle