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Michael Davis - One of the best experts on this subject based on the ideXlab platform.
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A Primary Acoustic Startle Pathway: Obligatory Role of Cochlear Root Neurons and the Nucleus Reticularis Pontis Caudalis
2013Co-Authors: Younglim Lee, Dolores E Lopez, Edward G Meloni, Michael DavisAbstract:Davis et al. (1982) proposed a primary acoustic startle circuit in rats consisting of the auditory nerve, posteroventral cochlear nucleus, an area near the ventrolateral lemniscus (VLL), nucleus Reticularis Pontis Caudalis (PnC), and spinal motoneurons. Using fiber-sparing lesions, the present study reevaluated these and other structures together with the role of neurons embedded in the auditory nerve [cochlear root neurons (CRNs)], recently hypothesized to be involved in acoustic startle. Small electrolytic lesions of the VLL or ventrolateral tegmental nucleus (VLTg) failed to eliminate startle. Large electrolytic lesions including the rostral ventral nucleus of the trapezoid body (rVNTB) and ventrolateral parts of PnC or lesions of the entire PnC blocked startle. However, small NMDA-induced lesions of the rVNTB failed to block startle, making it unlikely that the rVNTB itself is part of the startle pathway. In contrast, NMD
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Fear-potentiated startle in rats is mediated by neurons in the deep layers of the superior colliculus/deep mesencephalic nucleus of the rostral midbrain through the glutamate non-NMDA receptors.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2004Co-Authors: Zuowei Zhao, Michael DavisAbstract:The amygdala sends heavy and broad projections to the rostral midbrain including the periaqueductal gray (PAG), the deep layers of the superior colliculus/deep mesencephalic nucleus (deep SC/DpMe), and the lateral mesencephalic reticular formation (MRF) that in turn project to the nucleus Reticularis Pontis Caudalis (PnC), an obligatory relay in the primary acoustic startle circuit. Chemical lesions or inactivation of these areas blocked fear-potentiated startle, suggesting that these areas serve as a relay between the amygdala and the PnC. In the present study, we tried to determine more precisely which of these sites were critical for fear-potentiated startle and the role of glutamate receptors in this site in mediating fear-potentiated startle. Local infusion of the non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)-quinoxaline (NBQX) dose-dependently blocked fear-potentiated startle when infused into the deep SC/DpMe before testing but had no effect on baseline startle amplitude. NBQX did not block fear-potentiated startle when infused before training. The same dose of NBQX infused into the dorsal/lateral PAG, the lateral MRF, or the superficial layers of the SC did not affect fear-potentiated startle. However, NBQX tended to reduce contextual freezing when infused into the dorsal/lateral PAG. These findings suggest that the deep SC/DpMe is the site that serves as a critical output relay between the amygdala and the PnC in mediating fear-potentiated startle and that glutamatergic transmission is required for this action.
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muscimol in the deep layers of the superior colliculus mesencephalic reticular formation blocks expression but not acquisition of fear potentiated startle in rats
Behavioral Neuroscience, 1999Co-Authors: Edward G Meloni, Michael DavisAbstract:: Deposits of the retrograde tracer Fluoro-Gold into the ventrolateral nucleus Reticularis Pontis Caudalis labeled neurons in the deep layers of the superior colliculus/mesencephalic reticular formation (deep SC/Me). To test the involvement of this area in the fear-potentiated startle effect, rats were implanted with cannulas into the deep SC/Me and trained for fear-potentiated startle after infusion of the GABA(A) agonist muscimol (0.1 microg/0.5 microl). Two days later, they were tested for fear-potentiated startle. Rats then received a 2nd training session without any infusions, and 2 days later they were reinfused with muscimol (0.1 microg/0.5 microl) and tested for fear-potentiated startle. Local infusion of muscimol into the deep SC/Me completely blocked the expression but not the acquisition of fear-potentiated startle. These results indicate that a synapse in the midbrain is critical for the expression of fear-potentiated startle.
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Muscimol in the deep layers of the superior colliculus/mesencephalic reticular formation blocks expression but not acquisition of fear-potentiated startle in rats.
Behavioral neuroscience, 1999Co-Authors: Edward G Meloni, Michael DavisAbstract:Deposits of the retrograde tracer Fluoro-Gold into the ventrolateral nucleus Reticularis Pontis Caudalis labeled neurons in the deep layers of the superior colliculus/mesencephalic reticular formation (deep SC/Me). To test the involvement of this area in the fear-potentiated startle effect, rats were implanted with cannulas into the deep SC/Me and trained for fear-potentiated startle after infusion of the GABA(A) agonist muscimol (0.1 microg/0.5 microl). Two days later, they were tested for fear-potentiated startle. Rats then received a 2nd training session without any infusions, and 2 days later they were reinfused with muscimol (0.1 microg/0.5 microl) and tested for fear-potentiated startle. Local infusion of muscimol into the deep SC/Me completely blocked the expression but not the acquisition of fear-potentiated startle. These results indicate that a synapse in the midbrain is critical for the expression of fear-potentiated startle.
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The dorsal cochlear nucleus contributes to a high intensity component of the acoustic startle reflex in rats
Hearing research, 1998Co-Authors: Edward G Meloni, Michael DavisAbstract:The dorsal cochlear nucleus (DCN) has been shown to project to a region of the nucleus Reticularis Pontis Caudalis (PnC) critical for the evocation of startle in rats, suggesting a possible modulatory influence of the DCN on startle. This study examined the involvement of the DCN in the acoustic startle reflex and various other forms of behavioral plasticity seen with this response. Animals received bilateral electrolytic lesions of the DCN and were tested for acoustic startle responses, background noise facilitation, short-term habituation, prepulse inhibition and facilitation, and fear conditioning. Compared to sham lesioned rats, DCN lesioned rats showed a significant reduction in startle amplitude at the two highest startle-eliciting intensities (110 and 115 dB SPL) and normal responses on all other measures. Hence, the DCN appears to contribute to a high intensity component of the acoustic startle response in rats.
Edward G Meloni - One of the best experts on this subject based on the ideXlab platform.
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A Primary Acoustic Startle Pathway: Obligatory Role of Cochlear Root Neurons and the Nucleus Reticularis Pontis Caudalis
2013Co-Authors: Younglim Lee, Dolores E Lopez, Edward G Meloni, Michael DavisAbstract:Davis et al. (1982) proposed a primary acoustic startle circuit in rats consisting of the auditory nerve, posteroventral cochlear nucleus, an area near the ventrolateral lemniscus (VLL), nucleus Reticularis Pontis Caudalis (PnC), and spinal motoneurons. Using fiber-sparing lesions, the present study reevaluated these and other structures together with the role of neurons embedded in the auditory nerve [cochlear root neurons (CRNs)], recently hypothesized to be involved in acoustic startle. Small electrolytic lesions of the VLL or ventrolateral tegmental nucleus (VLTg) failed to eliminate startle. Large electrolytic lesions including the rostral ventral nucleus of the trapezoid body (rVNTB) and ventrolateral parts of PnC or lesions of the entire PnC blocked startle. However, small NMDA-induced lesions of the rVNTB failed to block startle, making it unlikely that the rVNTB itself is part of the startle pathway. In contrast, NMD
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muscimol in the deep layers of the superior colliculus mesencephalic reticular formation blocks expression but not acquisition of fear potentiated startle in rats
Behavioral Neuroscience, 1999Co-Authors: Edward G Meloni, Michael DavisAbstract:: Deposits of the retrograde tracer Fluoro-Gold into the ventrolateral nucleus Reticularis Pontis Caudalis labeled neurons in the deep layers of the superior colliculus/mesencephalic reticular formation (deep SC/Me). To test the involvement of this area in the fear-potentiated startle effect, rats were implanted with cannulas into the deep SC/Me and trained for fear-potentiated startle after infusion of the GABA(A) agonist muscimol (0.1 microg/0.5 microl). Two days later, they were tested for fear-potentiated startle. Rats then received a 2nd training session without any infusions, and 2 days later they were reinfused with muscimol (0.1 microg/0.5 microl) and tested for fear-potentiated startle. Local infusion of muscimol into the deep SC/Me completely blocked the expression but not the acquisition of fear-potentiated startle. These results indicate that a synapse in the midbrain is critical for the expression of fear-potentiated startle.
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Muscimol in the deep layers of the superior colliculus/mesencephalic reticular formation blocks expression but not acquisition of fear-potentiated startle in rats.
Behavioral neuroscience, 1999Co-Authors: Edward G Meloni, Michael DavisAbstract:Deposits of the retrograde tracer Fluoro-Gold into the ventrolateral nucleus Reticularis Pontis Caudalis labeled neurons in the deep layers of the superior colliculus/mesencephalic reticular formation (deep SC/Me). To test the involvement of this area in the fear-potentiated startle effect, rats were implanted with cannulas into the deep SC/Me and trained for fear-potentiated startle after infusion of the GABA(A) agonist muscimol (0.1 microg/0.5 microl). Two days later, they were tested for fear-potentiated startle. Rats then received a 2nd training session without any infusions, and 2 days later they were reinfused with muscimol (0.1 microg/0.5 microl) and tested for fear-potentiated startle. Local infusion of muscimol into the deep SC/Me completely blocked the expression but not the acquisition of fear-potentiated startle. These results indicate that a synapse in the midbrain is critical for the expression of fear-potentiated startle.
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The dorsal cochlear nucleus contributes to a high intensity component of the acoustic startle reflex in rats
Hearing research, 1998Co-Authors: Edward G Meloni, Michael DavisAbstract:The dorsal cochlear nucleus (DCN) has been shown to project to a region of the nucleus Reticularis Pontis Caudalis (PnC) critical for the evocation of startle in rats, suggesting a possible modulatory influence of the DCN on startle. This study examined the involvement of the DCN in the acoustic startle reflex and various other forms of behavioral plasticity seen with this response. Animals received bilateral electrolytic lesions of the DCN and were tested for acoustic startle responses, background noise facilitation, short-term habituation, prepulse inhibition and facilitation, and fear conditioning. Compared to sham lesioned rats, DCN lesioned rats showed a significant reduction in startle amplitude at the two highest startle-eliciting intensities (110 and 115 dB SPL) and normal responses on all other measures. Hence, the DCN appears to contribute to a high intensity component of the acoustic startle response in rats.
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a primary acoustic startle pathway obligatory role of cochlear root neurons and the nucleus Reticularis Pontis Caudalis
The Journal of Neuroscience, 1996Co-Authors: Younglim Lee, Dolores E Lopez, Edward G Meloni, Michael DavisAbstract:Davis et al. (1982) proposed a primary acoustic startle circuit in rats consisting of the auditory nerve, posteroventral cochlear nucleus, an area near the ventrolateral lemniscus (VLL), nucleus Reticularis Pontis Caudalis (PnC), and spinal motoneurons. Using fiber-sparing lesions, the present study reevaluated these and other structures together with the role of neurons embedded in the auditory nerve [cochlear root neurons (CRNs)], recently hypothesized to be involved in acoustic startle. Small electrolytic lesions of the VLL or ventrolateral tegmental nucleus (VLTg) failed to eliminate startle. Large electrolytic lesions including the rostral ventral nucleus of the trapezoid body (rVNTB) and ventrolateral parts of PnC or lesions of the entire PnC blocked startle. However, small NMDA-induced lesions of the rVNTB failed to block startle, making it unlikely that the rVNTB itself is part of the startle pathway. In contrast, NMDA lesions of the full extension of the ventrolateral part of the PnC blocked startle completely, suggesting that the ventrolateral part of the PnC is critically involved. Bilateral kainic acid lesions of CRNs also blocked the startle reflex completely, providing the first direct evidence for an involvement of CRNs in startle. This blockade probably was not caused by damage to the auditory nerve, because the lesioned animals showed intact compound action potentials recorded from the ventral cochlear nucleus. Hence, a primary acoustic startle pathway may involve three synapses onto (1) CRNs, (2) neurons in PnC, and (3) spinal motoneurons.
Mindy J.d. Miserendino - One of the best experts on this subject based on the ideXlab platform.
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NMDA and non-NMDA antagonists infused into the nucleus Reticularis Pontis Caudalis depress the acoustic startle reflex
Brain research, 1993Co-Authors: Mindy J.d. Miserendino, Michael DavisAbstract:Abstract The neural pathway that mediates the acoustic startle reflex has been proposed; however, the pharmacology underlying this reflex is less well known. The present study examined the role of excitatory amino acid receptors at the level of the nucleus Reticularis Pontis Caudalis, a brainstem nucleus obligatory for the whole body startle reflex and implicated as the locus where extrinsic systems such as the amygdala may act to modulate acoustic startle. Twenty-nine rats, chronically implanted with bilateral cannulae aimed at the nucleus Reticularis Pontis Caudalis, were tested to assess the effects of γ- d -glutamylglycine (DGG), dl -2-amino-5-phosphonopentanoic acid (AP5), and 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) on the amplitude of the acoustic startle reflex. Local infusion of each of the 3 compounds significantly reduced startle amplitude by as much as 70–80%. AP5 and CNQX attenuated startle over a dose range which indicated that the Reticularis Pontis Caudalis may be much more sensitive to these compounds than other nuclei along the primary startle pathway. These results suggest that, at the level of the nucleus Reticularis Pontis Caudalis, an excitatory amino acid neurotransmitter may mediate acoustic startle, and that both NMDA and non-NMDA receptor subtypes may be important for the expression of the acoustic startle reflex.
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A direct projection from the central nucleus of the amygdala to the acoustic startle pathway: anterograde and retrograde tracing studies.
Behavioral neuroscience, 1991Co-Authors: Jeffrey B. Rosen, Janice M Hitchcock, Catherine B Sananes, Mindy J.d. MiserendinoAbstract:Previous work has shown that lesions of the central nucleus of the amygdala block fear-potentiated acoustic startle and that electrical simulation of the central nucleus enhances acoustic startle in rats. In the present study, the anterograde tracer Phaseolus vulgaris-leucoagglutinin was used to identify and delineate the course of a direct projection from the central nucleus of the amygdala to the nucleus Reticularis Pontis Caudalis, a nucleus in the acoustic startle circuit. Experiments using the retrograde tracer Fluoro-Gold confirmed this and indicated that the rostral part of the medial subdivision of the central nucleus of the amygdala contains the cells that project to the startle circuit. With this information, lesion studies (see companion article Hitchcock & Davis, 1991) may be used to determine whether this projection plays a role in fear-potentiated startle.
Dolores E Lopez - One of the best experts on this subject based on the ideXlab platform.
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Direct and indirect nigrofugal projections to the nucleus Reticularis Pontis Caudalis mediate in the motor execution of the acoustic startle reflex.
Brain structure & function, 2018Co-Authors: Sebastian Hormigo, Dolores E Lopez, Antonio Cardoso, Gladys Zapata, Jacqueline Sepúlveda, Orlando CastellanoAbstract:The acoustic startle reflex (ASR) is a short and intense defensive reaction in response to a loud and unexpected acoustic stimulus. In the rat, a primary startle pathway encompasses three serially connected central structures: the cochlear root neurons, the giant neurons of the nucleus Reticularis Pontis Caudalis (PnC), and the spinal motoneurons. As a sensorimotor interface, the PnC has a central role in the ASR circuitry, especially the integration of different sensory stimuli and brain states into initiation of motor responses. Since the basal ganglia circuits control movement and action selection, we hypothesize that their output via the substantia nigra (SN) may interplay with the ASR primary circuit by providing inputs to PnC. Moreover, the pedunculopontine tegmental nucleus (PPTg) has been proposed as a functional and neural extension of the SN, so it is another goal of this study to describe possible anatomical connections from the PPTg to PnC. Here, we made 6-OHDA neurotoxic lesions of the SN pars compacta (SNc) and submitted the rats to a custom-built ASR measurement session to assess amplitude and latency of motor responses. We found that following lesion of the SNc, ASR amplitude decreased and latency increased compared to those values from the sham-surgery and control groups. The number of dopamine neurons remaining in the SNc after lesion was also estimated using a stereological approach, and it correlated with our behavioral results. Moreover, we employed neural tract-tracing techniques to highlight direct projections from the SN to PnC, and indirect projections through the PPTg. Finally, we also measured levels of excitatory amino acid neurotransmitters in the PnC following lesion of the SN, and found that they change following an ipsi/contralateral pattern. Taken together, our results identify nigrofugal efferents onto the primary ASR circuit that may modulate motor responses.
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A Primary Acoustic Startle Pathway: Obligatory Role of Cochlear Root Neurons and the Nucleus Reticularis Pontis Caudalis
2013Co-Authors: Younglim Lee, Dolores E Lopez, Edward G Meloni, Michael DavisAbstract:Davis et al. (1982) proposed a primary acoustic startle circuit in rats consisting of the auditory nerve, posteroventral cochlear nucleus, an area near the ventrolateral lemniscus (VLL), nucleus Reticularis Pontis Caudalis (PnC), and spinal motoneurons. Using fiber-sparing lesions, the present study reevaluated these and other structures together with the role of neurons embedded in the auditory nerve [cochlear root neurons (CRNs)], recently hypothesized to be involved in acoustic startle. Small electrolytic lesions of the VLL or ventrolateral tegmental nucleus (VLTg) failed to eliminate startle. Large electrolytic lesions including the rostral ventral nucleus of the trapezoid body (rVNTB) and ventrolateral parts of PnC or lesions of the entire PnC blocked startle. However, small NMDA-induced lesions of the rVNTB failed to block startle, making it unlikely that the rVNTB itself is part of the startle pathway. In contrast, NMD
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direct input from cochlear root neurons to pontine reticulospinal neurons in albino rat
The Journal of Comparative Neurology, 2003Co-Authors: Fernando R Nodal, Dolores E LopezAbstract:The cochlear root neurons (CRNs) are thought to mediate the auditory startle reflex (ASR) in the rat, which is widely used as a behavioral model for the investigation of the sensorimotor integration. CRNs project, among other targets, to the nucleus Reticularis Pontis Caudalis (PnC), a major component of the ASR circuit, but little is known about the organization of this projection. Thus, we injected biotinylated dextran amine (BDA) in CRNs to study their projections with light and electron microscopy. Also, we performed doublelabeling experiments, injecting BDA in the CRNs and subunit B of the cholera toxin or Fluorogold in the spinal cord to verify that CRNs project onto reticulospinal neurons. Electron microscopy of the labeled CRNs axons and terminals showed that even their most central and thinnest processes are myelinated. Most of the terminals are axodendritic, with multiple asymmetric synapses, and contain round vesicles (50 nm diameter). Double-labeling experiments demonstrated that CRN terminals are apposed to retrogradely labeled reticulospinal neurons in the contralateral nucleus Reticularis PnC and bilaterally in the lateral paragigantocellular nucleus. Analyses of serial sections revealed that multiple CRNs synapse on single reticulospinal neurons in PnC, suggesting a convergence of auditory information. The morphometric features of these neurons classify them as giant neurons. This study confirms that CRNs project directly onto reticulospinal neurons and presents other anatomical features of the CRNs that contribute to a better understanding of the circuitry of the ASR in the rat. J. Comp. Neurol. 460:80 –93, 2003. © 2003 Wiley-Liss, Inc. Indexing terms: acoustic startle reflex; reticular formation; biotinylated dextran amine; fluorogold; subunitB cholera toxin; nucleus Reticularis Pontis Caudalis
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Direct input from cochlear root neurons to pontine reticulospinal neurons in albino rat
The Journal of comparative neurology, 2003Co-Authors: Fernando R Nodal, Dolores E LopezAbstract:The cochlear root neurons (CRNs) are thought to mediate the auditory startle reflex (ASR) in the rat, which is widely used as a behavioral model for the investigation of the sensorimotor integration. CRNs project, among other targets, to the nucleus Reticularis Pontis Caudalis (PnC), a major component of the ASR circuit, but little is known about the organization of this projection. Thus, we injected biotinylated dextran amine (BDA) in CRNs to study their projections with light and electron microscopy. Also, we performed double-labeling experiments, injecting BDA in the CRNs and subunit B of the cholera toxin or Fluorogold in the spinal cord to verify that CRNs project onto reticulospinal neurons. Electron microscopy of the labeled CRNs axons and terminals showed that even their most central and thinnest processes are myelinated. Most of the terminals are axodendritic, with multiple asymmetric synapses, and contain round vesicles (50 nm diameter). Double-labeling experiments demonstrated that CRN terminals are apposed to retrogradely labeled reticulospinal neurons in the contralateral nucleus Reticularis PnC and bilaterally in the lateral paragigantocellular nucleus. Analyses of serial sections revealed that multiple CRNs synapse on single reticulospinal neurons in PnC, suggesting a convergence of auditory information. The morphometric features of these neurons classify them as giant neurons. This study confirms that CRNs project directly onto reticulospinal neurons and presents other anatomical features of the CRNs that contribute to a better understanding of the circuitry of the ASR in the rat.
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a primary acoustic startle pathway obligatory role of cochlear root neurons and the nucleus Reticularis Pontis Caudalis
The Journal of Neuroscience, 1996Co-Authors: Younglim Lee, Dolores E Lopez, Edward G Meloni, Michael DavisAbstract:Davis et al. (1982) proposed a primary acoustic startle circuit in rats consisting of the auditory nerve, posteroventral cochlear nucleus, an area near the ventrolateral lemniscus (VLL), nucleus Reticularis Pontis Caudalis (PnC), and spinal motoneurons. Using fiber-sparing lesions, the present study reevaluated these and other structures together with the role of neurons embedded in the auditory nerve [cochlear root neurons (CRNs)], recently hypothesized to be involved in acoustic startle. Small electrolytic lesions of the VLL or ventrolateral tegmental nucleus (VLTg) failed to eliminate startle. Large electrolytic lesions including the rostral ventral nucleus of the trapezoid body (rVNTB) and ventrolateral parts of PnC or lesions of the entire PnC blocked startle. However, small NMDA-induced lesions of the rVNTB failed to block startle, making it unlikely that the rVNTB itself is part of the startle pathway. In contrast, NMDA lesions of the full extension of the ventrolateral part of the PnC blocked startle completely, suggesting that the ventrolateral part of the PnC is critically involved. Bilateral kainic acid lesions of CRNs also blocked the startle reflex completely, providing the first direct evidence for an involvement of CRNs in startle. This blockade probably was not caused by damage to the auditory nerve, because the lesioned animals showed intact compound action potentials recorded from the ventral cochlear nucleus. Hence, a primary acoustic startle pathway may involve three synapses onto (1) CRNs, (2) neurons in PnC, and (3) spinal motoneurons.
M Davis - One of the best experts on this subject based on the ideXlab platform.
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Modulation of the acoustic startle reflex by infusion of corticotropin-releasing hormone into the nucleus Reticularis Pontis Caudalis.
Brain research, 1998Co-Authors: S G Birnbaum, M DavisAbstract:The amplitude of the acoustic startle reflex can be modulated by exposure to aversive stimuli or other conditions which evoke a state of fear. The neurotransmitters involved in this modulation are currently being investigated. Unilateral local infusion of corticotropin-releasing hormone (CRH; 0, 10, 20, 40 and 80 ng) into the nucleus Reticularis Pontis Caudalis (PnC), an obligatory synapse in the acoustic startle reflex, significantly elevated startle amplitude in a dose-dependent manner. The facilitation of startle began immediately following infusion, reached asymptote approximately 20-25 min later, and persisted throughout the remaining 60 min test session. This CRH-enhanced startle effect was blocked by infusion of the CRH antagonist, alpha-helical CRH9-41, immediately prior to CRH infusion. These results support an involvement of CRH at the level of the PnC in modulating the acoustic startle reflex.
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Involvement of cyclic AMP at the level of the nucleus Reticularis Pontis Caudalis in the acoustic startle response.
Brain research, 1995Co-Authors: T C De Lima, M DavisAbstract:Rats were implanted with cannulas in the nucleus Reticularis Pontis Caudalis (PnC), an obligatory part of the neural pathway that mediates the acoustic startle reflex. Following at least 1 week of recovery, rats were tested for acoustic startle amplitude before or after infusion of compounds known to alter the second messenger, adenosine cyclic 3', 5'-monophosphate (cAMP). Local infusion into the PnC of the cAMP analog, 8-bromo cAMP (0.125-1.0 micrograms), increased the amplitude of the acoustic startle response in a dose-dependent manner. In addition, local infusion of a phosphodiesterase inhibitor, rolipram (10 micrograms) or the water soluble adenylate cyclase activator, forskolin-DHA (2.5 micrograms), produced a significant enhancement of startle amplitude. These effects probably resulted from intracellular actions because cAMP itself, which does not readily penetrate lipid membranes, had no effect. Moreover, the effects seemed somewhat specific because the precursor of cAMP, ATP or 8-bromo cGMP, also failed to alter startle at doses where 8 bromo-cAMP did. The fact that a phosphodiesterase inhibitor elevated startle suggests that cAMP serves to tonically elevate startle at this level of the pathway. Hence, treatments that either increase (fear, sensitization) or decrease (habituation, pre-pulse inhibition) startle at the level of the PnC may do so via release of neurotransmitters either positively or negatively coupled to cAMP, which in turn may alter either sound evoked transmitter release, excitability of PnC neurons or both.