Isoproterenol potentiates synaptic transmission primarily by enhancing presynaptic calcium influx via P- and/or Q-type calcium channels in the rat amygdala

140

130

Substantial data exists demonstrating the importance of the amygdala and the locus ceruleus (LC) in responding to stress, aversive memory formation, and the development of stress-related disorders; however, little is known about the effects of norepinephrine (NE) on amygdala neuronal activity in vivo. The basolateral nucleus of the amygdala (BLA) receives dense NE projections from the LC, NE increases in the BLA in response to stress, and the BLA can also modulate the LC via reciprocal projections. These experiments examined the effects of noradrenergic agents on spontaneous and evoked responses of BLA neurons. NE iontophoresis inhibited spontaneous firing and decreased the responsiveness of BLA neurons to electrical stimulation of entorhinal cortex and sensory association cortex (Te3). Confirmed BLA projection neurons exhibited exclusively inhibitory responses to NE. Systemic administration of propranolol, a ␤-receptor antagonist, decreased the spontaneous firing rate and potentiated the NE-evoked inhibition of BLA neurons. In addition, iontophoresis of the ␣-2 agonist clonidine, footshock administration, and LC stimulation mimicked the effects of NE iontophoresis on spontaneous activity. Furthermore, the effects of LC stimulation were partially blocked by systemic administration of ␣ 2 and ␤ receptor antagonists. This is the first study to demonstrate the actions of directly applied and stimulus-evoked NE in the BLA in vivo, and provides a mechanism by which ␤ receptors can mediate the important behavioral consequences of NE within the BLA. The interaction between these two structures is particularly relevant with regard to their known involvement in stress responses and stress-related disorders.

Section: Discussionmentioning

confidence: 99%

Noradrenergic Modulation of Basolateral Amygdala Neuronal Activity: Opposing Influences of α-2 and β Receptor Activation

Buffalari

Grace²

2007

140

130

“…The possibility of some additional presynaptic effects of cholinergic drugs on PPRF axon terminals on PH neurons was also checked, using the paired-pulse paradigm (Mennerick and Zorumsky, 1995;Huang et al, 1996;Yajeya et al, 2000). It has been reported (Huang et al, 1996;Thompson, 2000;Fernández de Sevilla et al, 2002) that any change in the response evoked by the second stimulus (S2) in relation to the first (S1) will be indicative of a presynaptic action (100 ϫ S2/S1).…”

Section: Postsynaptic and Presynaptic Effects Of Cholinergic Drugs Onmentioning

confidence: 99%

“…It has been reported (Huang et al, 1996;Thompson, 2000;Fernández de Sevilla et al, 2002) that any change in the response evoked by the second stimulus (S2) in relation to the first (S1) will be indicative of a presynaptic action (100 ϫ S2/S1). Explored PH neurons (n ϭ 10) presented a reduction (61.00 Ϯ 0.03%) in EPSP amplitude evoked by the second stimulus (S2) presented to the PPRF in relation to the first (S1), at an interval of 50 -100 msec (Fig.…”

Section: Postsynaptic and Presynaptic Effects Of Cholinergic Drugs Onmentioning

confidence: 99%

A Cholinergic Synaptically Triggered Event Participates in the Generation of Persistent Activity Necessary for Eye Fixation

Navarro‐López¹,

Alvarado²,

Márquez-Ruiz³

et al. 2004

An exciting topic regarding integrative properties of the nervous system is how transient motor commands or brief sensory stimuli are able to evoke persistent neuronal changes, mainly as a sustained, tonic action potential firing. A persisting firing seems to be necessary for postural maintenance after a previous movement. We have studied in vitro and in vivo the generation of the persistent neuronal activity responsible for eye fixation after spontaneous eye movements. Rat sagittal brainstem slices were used for the intracellular recording of prepositus hypoglossi (PH) neurons and their synaptic activation from nearby paramedian pontine reticular formation (PPRF) neurons. Single electrical pulses applied to the PPRF showed a monosynaptic glutamatergic projection on PH neurons, acting on AMPA-kainate receptors. Train stimulation of the PPRF area evoked a sustained depolarization of PH neurons exceeding (by hundreds of milliseconds) stimulus duration. Both duration and amplitude of this sustained depolarization were linearly related to train frequency. The trainevoked sustained depolarization was the result of interaction between glutamatergic excitatory burst neurons and cholinergic mesopontine reticular fibers projecting onto PH neurons, because it was prevented by slice superfusion with cholinergic antagonists and mimicked by cholinergic agonists. As expected, microinjections of cholinergic antagonists in the PH nucleus of alert behaving cats evoked a gaze-holding deficit consisting of a re-centering drift of the eye after each saccade. These findings suggest that a slow, cholinergic, synaptically triggered event participates in the generation of persistent activity characteristic of PH neurons carrying eye position signals.

“…A primary mechanism by which cAMP regulates neural excitability is through the activation of cAMP-dependent protein kinase A (PKA). The neuromodulatory actions of PKA have been documented extensively and include altering ion channel activity (Nagel et al, 1992;Johnson et al, 1994;Surmeier et al, 1995), gene expression (Impey et al, 1996), and neurotransmitter release Huang et al, 1996). Although a considerable amount of information is known about the effects of PKA at the molecular and single channel levels, much remains to be determined about how its actions at a variety of sites may affect cytosolic Ca 2ϩ regulation in synaptically active neurons.…”

Section: Abstract: Mediobasal Hypothalamus; Calcium; Gaba; Gaba Excimentioning

confidence: 99%

GABA Activity Mediating Cytosolic Ca²⁺Rises in Developing Neurons Is Modulated by cAMP-Dependent Signal Transduction

Obrietan

Pol

1997

In the majority of developing neurons, GABA can exert depolarizing actions, thereby raising neuronal Ca 2ϩ . Ca 2ϩ elevations can have broad consequences during development, inducing gene expression, altering neurite outgrowth and growth cone turning, activating enzyme pathways, and influencing neuronal survival. We used fura-2 and fluo-3 Ca 2ϩ digital imaging to assess the effects of inhibiting or activating the cAMP signal transduction pathway on GABA activity mediating Ca 2ϩ rises during the early stages of in vitro hypothalamic neural development. Our experiments stemmed from the finding that stimulation of transmitter receptors shown to either activate or inhibit adenylyl cyclase activity caused a rapid decrease in Ca 2ϩ rises mediated by synaptically released GABA. Both the adenylyl cyclase activator forskolin and the inhibitor SQ-22,536 reduced the Ca 2ϩ rise elicited by the synaptic release of GABA. Bath application of the membrane-permeable cAMP analogs 8-bromo-cAMP (8-Br-cAMP) or 8-(4-chlorophenylthio)-cAMP (0.2-5 mM) produced a rapid, reversible, dose-dependent inhibition of Ca 2ϩ rises triggered by synaptic GABA release. Potentiation of GABAergic activity mediating Ca 2ϩ rises was observed in some neurons at relatively low concentrations of the membrane-permeable cAMP analogs (20 -50 M). In the presence of tetrodotoxin (TTX), postsynaptic Ca 2ϩ rises triggered by the bath application of GABA were only moderately depressed (13%) by 8-Br-cAMP (1 mM), suggesting that the inhibitory effects of 8-Br-cAMP were largely the result of a presynaptic mechanism.The protein kinase A (PKA) inhibitors H89 and Rp-3Ј,5Ј-cyclic monophosphothioate triethylamine also caused a large reduction (Ͼ70%) in Ca 2ϩ rises triggered by synaptic GABA release. Unlike the short-term depression elicited by activation of the cAMP signal transduction pathway, Ca 2ϩ depression elicited by PKA inhibition persisted for an extended period (Ͼ30 min) after PKA inhibitor washout. Postsynaptic depression of GABA-evoked Ca 2ϩ rises triggered by H89 (in the presence of TTX) recovered rapidly, suggesting that the extended depression observed during synaptic GABA release was largely through a presynaptic mechanism. Long-term Ca 2ϩ modulation by cAMP-regulating hypothalamic peptides may be mediated through a parallel mechanism.Together, these results suggest that GABAergic activity mediating Ca 2ϩ rises is dependent on ongoing PKA activity that is maintained within a narrow zone for GABA to elicit a maximal Ca 2ϩ elevation. Thus, neuromodulator-mediated changes in the cAMP-dependent signal transduction pathway (activation or inhibition) could lead to a substantial decrease in GABAmediated Ca 2ϩ rises during early development.