Synaptic Interactions Underlying Synchronized Inhibition in the Basal Amygdala: Evidence for Existence of Two Types of Projection Cells

Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, New Jersey 07102, USA.
Journal of Neurophysiology (Impact Factor: 2.89). 11/2010; 105(2):687-96. DOI: 10.1152/jn.00732.2010
Source: PubMed


The basal amygdala (BA) plays a key role in mediating the facilitating effects of emotions on memory. Recent findings indicate that this function depends on the ability of BA neurons to generate coherent oscillatory activity, facilitating synaptic plasticity in target neurons. However, the mechanisms allowing BA neurons to synchronize their activity remain poorly understood. Here, we aimed to shed light on this question, focusing on a slow periodic inhibitory oscillation previously observed in the BA in vitro. Paired patch recordings showed that these large inhibitory postsynaptic potentials (IPSPs) occur almost synchronously in BA projection neurons, that they were typically not preceded by excitatory postsynaptic potentials (EPSPs), and that they had little or no correlate in neighboring amygdala nuclei or cortical fields. The initial phase of the IPSPs was associated with an increase in membrane potential fluctuations at 50-100 Hz. In keeping with this, the IPSPs seen in projection cells were correlated with repetitive firing at 50-100 Hz in presumed interneurons and they could be abolished by picrotoxin. However, the IPSPs were also sensitive to 6-cyano-7-nitroquinoxaline-2,3-dione, implying that they arose from the interplay between glutamatergic and GABAergic BA neurons. In support of this idea, we identified a small subset of projection cells (15%), positively identified as such by retrograde labeling from BA projection sites, that began firing shortly before the IPSP onset and presumably drove interneuronal firing. These results add to a rapidly growing body of data indicating that the BA contains at least two distinct types of projection cells that vary in their relation with interneurons and extra-amygdala targets.

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    • "Our data are consistent with this finding because presentation of a tone predicting a footshock significantly increased c-Fos expression in BA PVINs in WT mice. PVINs target the perisomatic region of PNs (Bienvenu et al, 2012), inhibiting and synchronizing their firing (Popescu and Paré, 2011; Ryan et al, 2012; Woodruff and Sah, 2007) and disinhibiting their dendrites (Wolff et al, 2014). Hence, they tightly control the BLA output to the central amygdala, orchestrating fear responses. "
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    ABSTRACT: Genetic association studies suggest that variations in the 5-hydroxytryptamine (5-HT; serotonin) transporter (5-HTT) gene are associated with susceptibility to psychiatric disorders such as anxiety or post-traumatic stress disorder. Individuals carrying high 5-HTT expressing gene variants display low amygdala reactivity to fearful stimuli. Mice overexpressing the 5-HTT (5-HTTOE), an animal model of this human variation, show impaired fear, together with reduced fear-evoked theta oscillations in the basolateral amygdala (BLA). However, it is unclear how variation in 5-HTT gene expression impacts on the microcircuitry of the BLA to change behavior. We addressed this issue by investigating the activity of parvalbumin (PV)-expressing interneurons (PVINs), the biggest interneuron population in the basal amygdala (BA). We found that increased 5-HTT expression impairs the recruitment of PVINs (measured by their c-Fos immunoreactivity) during fear. Ex vivo patch-clamp recordings demonstrated that the depolarizing effect of 5-HT on PVINs was mediated by 5-HT2A receptor. In 5-HTTOE mice, 5-HT-evoked depolarization of PVINs and synaptic inhibition of principal cells, which provide the major output of the BA, were impaired. This deficit was due to reduced 5-HT2A function and not to increased 5-HT uptake. Collectively, these findings provide novel cellular mechanisms that are likely to contribute to differences in emotional behaviors linked with genetic variations of the 5-HTT.Neuropsychopharmacology accepted article preview online, 08 June 2015. doi:10.1038/npp.2015.157.
    Full-text · Article · Jun 2015 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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    • "The examination of neural inhibition continues, and current neurophysiology examines inhibition in relation to sensory adaptation [12], neural oscillations [13] and neuroscience of behavior [14]. Simpler networks rely on inhibition [15] and central nervous system 'gating' via inhibition is critical at every level from spinal cord (e.g., pain, [16]) to cerebellum [17] to midbrain [18] to different forebrain regions (cortex: [19]; striatum: [20] 2002; hippocampus: [21]; amygdala: [22]). A gating function is common to all inhibitory mechanisms. "
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    ABSTRACT: Integrating research efforts using a cross-domain approach could redefine traditional constructs used in behavioral and clinical neuroscience by demonstrating that behavior and mental processes arise not from functional isolation but from integration. Our research group has been examining the interface between cognitive and emotional processes by studying inhibitory gating. Inhibitory gating can be measured via changes in behavior or neural signal processing. Sensorimotor gating of the startle response is a well-used measure. To study how emotion and cognition interact during startle modulation in the animal model, we examined ultrasonic vocalization (USV) emissions during acoustic startle and prepulse inhibition. We found high rates of USV emission during the sensorimotor gating paradigm and revealed links between prepulse inhibition (PPI) and USV emission that could reflect emotional and cognitive influences. Measuring inhibitory gating as P50 event-related potential suppression has also revealed possible connections between emotional states and cognitive processes. We have examined the single unit responses during the traditional gating paradigm and found that acute and chronic stress can alter gating of neural signals in regions such as amygdala, striatum and medial prefrontal cortex. Our findings point to the need for more cross-domain research on how shifting states of emotion can impact basic mechanisms of information processing. Results could inform clinical work with the development of tools that depend upon cross-domain communication, and enable a better understanding and evaluation of psychological impairment.
    Full-text · Article · May 2014 · Behavioural Brain Research
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    • "PV+ interneurons have several characteristics that enable them to influence the activity of large networks of BLA principal neurons synchronously: first, these interneurons make up approximately 40% of the total interneuron population and are distributed throughout the BLA; second, each PV+ interneuron can innervate the soma and axon hillock of approximately 150 principal neurons [22]; finally, these interneurons are coupled electrically by gap junctions to create a functional syncytium [23]–[25]. Significantly, we and others have shown that, in paired recordings of rat BLA principal neurons, spontaneous IPSPs are highly synchronized [26], [27], suggesting that the output of PV+ interneurons may coordinate the activity of large numbers of principal neurons. "
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    ABSTRACT: The basolateral complex of the amygdala (BLA) is a critical component of the neural circuit regulating fear learning. During fear learning and recall, the amygdala and other brain regions, including the hippocampus and prefrontal cortex, exhibit phase-locked oscillations in the high delta/low theta frequency band (∼2-6 Hz) that have been shown to contribute to the learning process. Network oscillations are commonly generated by inhibitory synaptic input that coordinates action potentials in groups of neurons. In the rat BLA, principal neurons spontaneously receive synchronized, inhibitory input in the form of compound, rhythmic, inhibitory postsynaptic potentials (IPSPs), likely originating from burst-firing parvalbumin interneurons. Here we investigated the role of compound IPSPs in the rat and rhesus macaque BLA in regulating action potential synchrony and spike-timing precision. Furthermore, because principal neurons exhibit intrinsic oscillatory properties and resonance between 4 and 5 Hz, in the same frequency band observed during fear, we investigated whether compound IPSPs and intrinsic oscillations interact to promote rhythmic activity in the BLA at this frequency. Using whole-cell patch clamp in brain slices, we demonstrate that compound IPSPs, which occur spontaneously and are synchronized across principal neurons in both the rat and primate BLA, significantly improve spike-timing precision in BLA principal neurons for a window of ∼300 ms following each IPSP. We also show that compound IPSPs coordinate the firing of pairs of BLA principal neurons, and significantly improve spike synchrony for a window of ∼130 ms. Compound IPSPs enhance a 5 Hz calcium-dependent membrane potential oscillation (MPO) in these neurons, likely contributing to the improvement in spike-timing precision and synchronization of spiking. Activation of the cAMP-PKA signaling cascade enhanced the MPO, and inhibition of this cascade blocked the MPO. We discuss these results in the context of spike-timing dependent plasticity and modulation by neurotransmitters important for fear learning, such as dopamine.
    Full-text · Article · Apr 2012 · PLoS ONE
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