COUP-TFII controls amygdala patterning by regulating neuropilin expression

The development of the progenitor zones in the pallium, lateral ganglionic eminence (LGE) and medial ganglionic eminence (MGE) in the subpallium has been well studied; however, so far the role of the caudal ganglionic eminence (CGE), a posterior subpallial domain, in telencephalon patterning remains poorly understood. COUP-TFII, an orphan nuclear receptor, is preferentially expressed in the CGE. We generated COUP-TFII mouse mutants, using Rx-Cre (RxCre;COUP-TFII(F/F)), to study its function in telencephalon development. In these mutants, we found severe defects in the formation of the amygdala complex, including the lateral (LA), basolateral (BLA) and basomedial (BMA) amygdala nuclei. Molecular analysis provided evidence that the migration of CGE-derived Pax6(+) cells failed to settle into the BMA nucleus, owing to reduced expression of neuropilin 1 (Nrp1) and Nrp2, two semaphorin receptors that regulate neuronal cell migration and axon guidance. Our ChIP assays revealed that Nrp1 and Nrp2 genes are the direct targets of COUP-TFII in the telencephalon in vivo. Furthermore, our results showed that the coordinated development between the CGE originated subpallial population (Pax6(+) cells) and pallial populations (Tbr1(+) and Lhx2(+) cells) was essential for patterning the amygdala assembly. Our study presented novel genetic evidence that the caudal ganglionic eminence, a distinct subpallial progenitor zone, contributes cells to the basal telencephalon, such as the BMA nucleus.     

Curbing fear by axonal oxytocin release in the amygdala

Oxytocin produces anxiolytic effects via the central nucleus of the amygdala but how the peptide reaches its receptors in this region has been unclear. In this issue of Neuron, Knobloch et?al. (2012) demonstrate that evoked oxytocin release from axon terminals within the central amygdala results in attenuation of fear.     

The amygdala and reward

The amygdala -- an almond-shaped group of nuclei at the heart of the telencephalon -- has been associated with a range of cognitive functions, including emotion, learning, memory, attention and perception. Most current views of amygdala function emphasize its role in negative emotions, such as fear, and in linking negative emotions with other aspects of cognition, such as learning and memory. However, recent evidence supports a role for the amygdala in processing positive emotions as well as negative ones, including learning about the beneficial biological value of stimuli. Indeed, the amygdala's role in stimulus-reward learning might be just as important as its role in processing negative affect and fear conditioning.     

Hippocampus and amygdala neurotoxicity produced by systemic lidocaine in adult rats

There is evidence that using lidocaine-treated cellular culture produces cell damage. However, there are no studies in vivo demonstrating the potential injurious effect of lidocaine on the central nervous system. Therefore, the aim of our study was to investigate if lidocaine is involved in neuronal damage in the CA3 hippocampus and amygdala regions when using a single subconvulsive or a convulsive lidocaine dose. Two-month-old male Wistar rats (57) were used. The animals were randomly assigned to one of three groups. Group I received 0.9% saline ip (n=9), group II received a single lidocaine dose of 60 mg/kg (n=18), and group III received 90 mg/kg ip (n=12). At day 2, 7, and 10 after the dosing, three to six rats per group were sacrificed. The brains of the rats were removed and were embedded in paraffin. Coronal cuts of 7 microm were made. Each brain section was stained with cresyl-eosin. We evaluated the number of normal and abnormal neurons in the hippocampal CA3 (pyramidal) and basolateral amygdala (large and medium neurons) regions in a 10,000 microm2 section. To explore an association between lidocaine-induced seizure and neuronal damage, diazepam was used (10 mg/kg ig) as an anticonvulsant two hours before a 90 mg/kg dose of lidocaine. Lidocaine causes a morphological neuronal alteration in the CA3 hippocampal region and the basolateral amygdala and possibly an inhibition-excitation imbalance. Diazepam prevents lidocaine-induced seizures, but not neuronal damage in brain structures. Interaction of lidocaine with the membrane components produces disrupted Ca+2 homeostasis and causes neuronal damage. Moreover, it is possible that lidocaine or its metabolites could actively participate in the neuronal damage observed.     

Diverse processing of pharmacological and natural rewards by the central amygdala

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Basolateral amygdala neurons facilitate reward-seeking behavior by exciting nucleus accumbens neurons

Both the nucleus accumbens (NAc) and basolateral amygdala (BLA) contribute to learned behavioral choice. Neurons in both structures that encode reward-predictive cues may underlie the decision to respond to such cues, but the neural circuits by which the BLA influences reward-seeking behavior have not been established. Here, we test the hypothesis that the BLA drives NAc neuronal responses to reward-predictive cues. First, using a disconnection experiment, we show that the BLA and dopamine projections to the NAc interact to promote the reward-seeking behavioral response. Next, we demonstrate that BLA neuronal responses to cues precede those of NAc neurons and that cue-evoked excitation of NAc neurons depends on BLA input. These results indicate that BLA input is required for dopamine to enhance the cue-evoked firing of NAc neurons and that this enhanced firing promotes reward-seeking behavior.     

GABAergic neurons: gate masters of the amygdala, mastered by dopamine

A hyperdopaminergic state, such as stress, is associated with an increase in affective behavior. In this issue of Neuron, Marowsky and colleagues identify two clusters of paracapsular intercalated GABA neurons in amygdala slice preparations of GAD67-GFP mice. These GABA neurons mediate inhibition from cortical afferents to both the major input and output station of the amygdala, are inhibited during action of dopamine via D1 receptors, and are thus likely to represent important cellular players during dopaminergic disinhibition related to increased affective behavior.     

Glucose and lactate utilization by the amygdala of male and female rats

Gonadal hormones appear to modulate brain energy metabolism, and morphological and functional sexual differences are found in the amygdaloid complex (AC) of rats. Our aim was to study the CO₂ production and lipid synthesis, measured by the rate of L-[U-¹⁴C]lactate or D-[U-¹⁴C]glucose utilization (in pmol.hr^–1.mg^–1), by AC slices in vitro of male and female rats. Lactate was more used than glucose as energy substrate (p < 0.01) but no sex-related difference was observed in glucose or lactate oxidation to CO₂ (p > 0.05) or on lipid synthesis obtained from both substrates (p > 0.05). In addition, there was no effect of the estrous cycle on lactate oxidation to CO₂ by the AC of females (p > 0.05). Based on the present data, it appears that the endogenous normal levels of gonadal hormones are not able to promote sex-related differences in the in vitro glucose or lactate utilization by the AC of rats.     

Influence of passive avoidance learning by substance P in the basolateral amygdala

Neuropeptide substance P (SP) has reinforcing and memory facilitating effects after its peripheral or central application. Rats self-inject SP into the ventromedial caudate-putamen and SP microinjections into the basal forebrain induce place preference with a simultaneous increase of dopamine level. In the amygdaloid body SP positive neurones and terminals have been identified. The aim of the present study was to examine the possible reinforcing effects of SP in the basolateral amygdala (ABL). CFY male rats were conditioned in two-compartment passive avoidance paradigm and place preference was examined in two-compartment-box and in circular open field. Animals were microinjected bilaterally with 10 ng SP, 100 ng SP or vehicle solution (0.4 microl/side) into the ABL. Results showed that post-shock infusion of 10 ng SP significantly enhanced passive avoidance learning while 100 ng SP was ineffective. In two-compartment-box and in circular open field place preference did not develop after SP treatments, however. Our data are the first to demonstrate that SP in the ABL is involved in learning and memory processes related to aversive situations. Results that SP microinjections were not followed by rewarding-reinforcing consequences in place preference paradigms indicate that the local SP network in the ABL is not involved in neuronal circuitry responsible for addictive behaviour.     

Mitophagy in the basolateral amygdala mediates increased anxiety induced by aversive social experience

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Role of the amygdala in the sedation induced by low doses of apomorphine

In the present study the role of amygdala in the antidepressant action of imipramine is discussed. An animal model of depression is induced, in rats, by systemic injection of low doses of apomorphine. Systemic administration of imipramine prevents, as already reported, apomorphine-induced sedation. The same effect is observed following intra-amygdaloid imipramine administration. On the contrary, local injection of imipramine in frontal cortex or caudate nucleus does not affect apomorphine-induced sedation.     

Capsaicin-induced changes in LTP in the lateral amygdala are mediated by TRPV1

The transient receptor potential vanilloid type 1 (TRPV1) channel is a well recognized polymodal signal detector that is activated by painful stimuli such as capsaicin. Here, we show that TRPV1 is expressed in the lateral nucleus of the amygdala (LA). Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala. Capsaicin specifically changed the magnitude of long-term potentiation (LTP) in the LA in brain slices of mice depending on the anesthetic (ether, isoflurane) used before euthanasia. After ether anesthesia, capsaicin had a suppressive effect on LA-LTP both in patch clamp and in extracellular recordings. The capsaicin-induced reduction of LTP was completely blocked by the nitric oxide synthase (NOS) inhibitor L-NAME and was absent in neuronal NOS as well as in TRPV1 deficient mice. The specific antagonist of cannabinoid receptor type 1 (CB1), AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis. After isoflurane anesthesia before euthanasia capsaicin caused a TRPV1-mediated increase in the magnitude of LA-LTP. Therefore, our results also indicate that the appropriate choice of the anesthetics used is an important consideration when brain plasticity and the action of endovanilloids will be evaluated. In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms.