The basolateral amygdala (BLA) is believed to be involved in schizophrenia, depression, and other disorders that display affective components. The neuronal activity of the BLA, and BLA-mediated affective behaviors, are driven by sensory stimuli transmitted in part from sensory association cortical regions. These same behaviors may be regulated by prefrontal cortical (PFC) inputs to the BLA. However, it is unclear how two sets of glutamatergic inputs to the BLA can impose opposing actions on BLA-mediated behaviors; specifically, it is unclear how PFC inputs exert inhibitory actions over BLA projection neurons. Dopamine (DA) receptor activation enhances BLA-mediated behaviors. Although we have demonstrated that DA suppresses medial PFC inputs to the BLA and enhances sensory cortical inputs, the precise cellular mechanisms for its actions are unknown. In this study we use in vivo intracellular recordings to determine the means by which glutamatergic inputs from the PFC inhibit BLA projection neurons, contrast that with glutamatergic inputs from the association sensory cortex (Te3) that drive BLA projection neurons, and examine the effects of DA receptor activation on neuronal excitability, spontaneous postsynaptic potentials (PSPs), and PFC-evoked PSPs. We found that PFC stimulation inhibits BLA projection neurons by three mechanisms: chloride-mediated hyperpolarization, a persistent decrease in neuronal input resistance, and shunting of PSPs; all effects are possibly attributable to recruitment of inhibitory interneurons. DA receptor activation enhanced neuronal input resistance by a postsynaptic mechanism (via DA D2 receptors), suppressed spontaneously occurring and PFC-evoked PSPs (via DA D1 receptors), and enhanced Te3-evoked PSPs.

Pavlovian conditioning results when an innocuous stimulus, such as an odour, is paired with a behaviourally relevant stimulus, such as a foot-shock, so that eventually the former stimulus alone will elicit the behavioural response of the latter. The lateral nucleus of the amygdala (LAT) is necessary for the emotional memory formation in this paradigm. Enhanced neuronal firing in LAT to conditioned stimuli emerge in parallel with the behavioural changes and are dependent on local dopamine. To study the changes in neuronal excitability and synaptic drive that contribute to the pavlovian conditioning process, here we used in vivo intracellular recordings to examine LAT neurons during pavlovian conditioning in rats. We found that repeated pairings of an odour with a foot-shock resulted in enhanced post-synaptic potential (PSP) responses to the odour and increased neuronal excitability. However, a non-paired odour displayed PSP decrement. The dopamine antagonist haloperidol blocked the PSP enhancement and associated increased neuronal excitability, without reversing previous conditioning. These results demonstrate that conditioning and habituation processes produce opposite effects on LAT neurons and that dopamine is important in these events, consistent with its role in emotional memory formation.

The amygdala plays a role in learning and memory processes that involve an emotional component. However, neural structures that regulate these amygdala-dependent processes are unknown. Previous studies indicate that regulation of affect may be imposed by the prefrontal cortex (PFC) and its efferents to the amygdala. The presentation of conditioned affective stimuli enhances activity of neurons in the lateral nucleus of the amygdala (LAT), which is thought to drive conditioned affective responses. Moreover, plasticity of LAT neuronal responses to stimuli during the course of conditioning is believed to underlie affective learning. This study examines the role of the PFC in the regulation of affective behaviors by evaluating how the PFC affects LAT neuronal plasticity and activity that is evoked by previously conditioned stimuli. In vivo intracellular recordings were performed from the LAT of anesthetized rats during pavlovian conditioning and during the presentation of stimuli that were conditioned in the awake rat before recording. Train stimulation of the PFC suppressed LAT neuronal activity that was evoked by both previously conditioned and neutral stimuli. In addition, PFC stimulation blocked LAT neuronal plasticity associated with an affective conditioning procedure. These results indicate that the PFC has the potential to regulate affective processes by inhibition of the LAT. Patients with disruptions of the PFC-LAT interaction often display an inability to regulate affective responses. This may be attributable to the loss of PFC-imposed inhibition of the emotional response to a stimulus but may also include the formation or diminished extinction of inappropriate associations.

The basolateral complex of the amygdala (BLA) plays a significant role in affective behavior that is likely regulated by afferents from the medial prefrontal cortex (mPFC). Studies suggest that dopamine (DA) is a necessary component for production of appropriate affective responses. In this study, prefrontal cortical and sensory cortical [temporal area 3 (Te3)] inputs to the BLA and their modulation by DA receptor activation was examined using in vivo single-unit extracellular recordings. We found that Te3 inputs are more capable of driving BLA projection neuron firing, whereas mPFC inputs potently elicited firing from BLA interneurons. Moreover, mPFC stimulation before Te3 stimulation attenuated the probability of Te3-evoked spikes in BLA projection neurons, possibly via activation of inhibitory interneurons. DA receptor activation by apomorphine attenuated mPFC inputs, while augmenting Te3 inputs. Additionally, DA receptor activation suppressed mPFC-induced inhibition of Te3-evoked spikes. Thus, the mPFC may attenuate sensorydriven amygdala-mediated affective responses via recruitment of BLA inhibitory interneurons that suppress sensory cortical inputs. In situations of enhanced DA levels in the BLA, such as during stress and after amphetamine administration, mPFC regulation of BLA will be dampened, leading to a disinhibition of sensory-driven affective responses. : dopamine; amygdala; prefrontal cortex; temporal area 3; Te3; electrophysiology Disorders of the nervous system that include an affective component are believed to involve dysfunction within the amygdala. Thus, evidence of morphological or functional abnormalities of the amygdala have been found in schizophrenia, depression, anxiety, and temporal lobe epilepsy (Breier et al Key words

Background-Chronic stress is a major health concern, often leading to depression, anxiety or when severe enough, post-traumatic stress disorder (PTSD). While many studies demonstrate that the amygdala is hyper-responsive in patients with these disorders, the cellular neurophysiological effects of chronic stress on the systems that underlie psychiatric disorders, such as the amygdala, are relatively unknown.

. Dopamine modulates excitability of basolateral amygdala neurons in vitro. J Neurophysiol 93: 1598 -1610, 2005. First published November 10, 2004; doi:10.1152/jn.00843.2004. The amygdala plays a role in affective behaviors, which are modulated by the dopamine (DA) innervation of the basolateral amygdala complex (BLA). Although in vivo studies indicate that activation of DA receptors alters BLA neuronal activity, it is unclear whether DA exerts direct effects on BLA neurons or whether it acts via indirect effects on BLA afferents. Using whole cell patch-clamp recordings in rat brain slices, we investigated the site and mechanisms through which DA regulates the excitability of BLA neurons. Dopamine enhanced the excitability of BLA projection neurons in response to somatic current injections via a postsynaptic effect. Dopamine D1 receptor activation increased excitability and evoked firing, whereas D2 receptor activation increased input resistance. Current-and voltage-clamp experiments in projection neurons showed that D1 receptor activation enhanced excitability by modulating a 4-aminopyridine-and ␣-dendrotoxin-sensitive, slowly inactivating K ϩ current. Furthermore, DA and D1 receptor activation increased evoked firing in fast-spiking BLA interneurons. Consistent with a postsynaptic modulation of interneuron excitability, DA also increased the frequency of spontaneous inhibitory postsynaptic currents recorded in projection neurons without changing release of GABA. These data demonstrate that DA exerts direct effects on BLA projection neurons and indirect actions via modulation of interneurons that may work in concert to enhance the neuronal response to large, suprathreshold inputs, while suppressing weaker inputs. Some of the enhancing effects of DA on affective behaviors may be explained by cellular actions of DA on BLA neurons. Systemic or iontophoretic administration of DA agonists alters the firing rate of BLA projection neurons and interneurons (Bashore et al. 1978; Ben-Ari and Kelly 1976;Rosenkranz and Grace 1999;Spehlmann and Norcross 1984). However, systemic administrations of DA receptor agonists also exert actions on synaptic inputs to the BLA Grace 2001, 2002a). Thus in these previous studies, it was difficult to exclude indirect effects of DA on BLA neurons via actions on afferent regions. Therefore in this study we utilized in vitro whole cell recordings from rat brain slices to test the hypothesis that DA exerts direct postsynaptic actions that alter BLA neuronal excitability, which could account for the effects observed in vivo with systemic administration of DA agonists, and to determine the receptor subtypes involved in these actions of DA.Our data show that DA increases the excitability of BLA projection neurons via mechanisms involving both D1 and D2 receptors and also increases evoked and spontaneous spike firing in fast-spiking interneurons. In projection neurons, the D1 receptor-dependent increase in excitability was due to the reduction in an outward-rectifying, 4-aminopyridine (4-AP) an...

The basolateral amygdala (BLA) is implicated in responding to affective stimuli. Dopamine (DA) is released in the BLA during numerous conditions; however, the neurophysiological effects of DA in the BLA have not been examined in depth. In this study, the effects of DA receptor manipulation on spontaneous and afferent-driven neuronal firing were examined using in vivo extracellular single-unit recordings in parallel with systemic and iontophoretic drug application, and stimulation of the substantia nigra/ventral tegmental area in the rat. The effects of DA receptor activation in the BLA were found to depend on the characteristics of the BLA neuron examined, causing an increase in the firing rate of putative interneurons and a decrease in the firing of identified projection neurons. Additionally, DA receptor activation attenuated short-latency spikes evoked by electrical stimulation of prefrontal cortical and mediodorsal thalamic inputs to the BLA while potentiating the responses evoked by electrical stimulation of sensory association cortex. DA receptor activation can thus attenuate BLA projection neuron firing via two mechanisms: (1) by a direct inhibition, and (2) by indirect actions mediated via activation of BLA interneurons. This is hypothesized to lead to a global filtration of weaker inputs. Moreover, DA potentiates sensory inputs and attenuates medial prefrontal cortex inputs to the BLA. Conditions in which DA is released in the BLA, such as during the presentation of an affective stimulus, will lead to a potentiation of the strongest sensory input and a dampening of cortical inhibition over the BLA, thus augmenting the response to affective sensory stimuli.

Depression and anxiety are diagnosed almost twice as often in women, and the symptomology differs in men and women and is sensitive to sex hormones. The basolateral amygdala (BLA) contributes to emotion-related behaviors that differ between males and females and across the reproductive cycle. This hints at sex- or estrus-dependent features of BLA function, about which very little is known. The purpose of this study was to test whether there are sex differences or estrous cyclicity in rat BLA physiology and to determine their mechanistic correlates. We found substantial sex differences in the activity of neurons in lateral nuclei (LAT) and basal nuclei (BA) of the BLA that were associated with greater excitatory synaptic input in females. We also found strong differences in the activity of LAT and BA neurons across the estrous cycle. These differences were associated with a shift in the inhibition-excitation balance such that LAT had relatively greater inhibition during proestrus which paralleled more rapid cued fear extinction. In contrast, BA had relatively greater inhibition during diestrus that paralleled more rapid contextual fear extinction. These results are the first to demonstrate sex differences in BLA neuronal activity and the impact of estrous cyclicity on these measures. The shift between LAT and BA predominance across the estrous cycle provides a simple construct for understanding the effects of the estrous cycle on BLA-dependent behaviors. These results provide a novel framework to understand the cyclicity of emotional memory and highlight the importance of considering ovarian cycle when studying the BLA of females. There are differences in emotional responses and many psychiatric symptoms between males and females. This may point to sex differences in limbic brain regions. Here we demonstrate sex differences in neuronal activity in one key limbic region, the basolateral amygdala (BLA), whose activity fluctuates across the estrous cycle due to a shift in the balance of inhibition and excitation across two BLA regions, the lateral and basal nuclei. By uncovering this push-pull shift between lateral and basal nuclei, these results help to explain disparate findings about the effects of biological sex and estrous cyclicity on emotion and provide a framework for understanding fluctuations in emotional memory and psychiatric symptoms.