Basolateral Amygdala Projection Research Articles

Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking

The basolateral amygdala (BLA) plays a crucial role in emotional learning irrespective of valence1–5. While the BLA projection to the nucleus accumbens (NAc) is hypothesized to modulate cue-triggered motivated behaviors4, 6, 7,, our understanding of the interaction between these two brain regions has been limited by the inability to manipulate neural circuit elements of this pathway selectively during behavior. To circumvent this limitation, we used in vivo optogenetic stimulation or inhibition of glutamatergic fibers from the BLA to the NAc, coupled with intracranial pharmacology and ex vivo electrophysiology. We show that optical stimulation of the BLA-to-NAc pathway in mice reinforces behavioral responding to earn additional optical stimulations of these synaptic inputs. Optical stimulation of BLA-to-NAc glutamatergic fibers required intra-NAc dopamine D1-type, but not D2-type, receptor signaling. Brief optical inhibition of BLA-to-NAc fibers reduced cue-evoked intake of sucrose, demonstrating an important role of this specific pathway in controlling naturally occurring reward-related behavior. Moreover, while optical stimulation of medial prefrontal cortex (mPFC) to NAc glutamatergic fibers also elicited reliable excitatory synaptic responses, optical self-stimulation behavior was not observed by activation of this pathway. These data suggest that while the BLA is important for processing both positive and negative affect, the BLA-to-NAc glutamatergic pathway in conjunction with dopamine signaling in the NAc promotes motivated behavioral responding.

Location and Function of the Slow Afterhyperpolarization Channels in the Basolateral Amygdala

The basolateral amygdala (BLA) assigns emotional significance to sensory stimuli. This association results in a change in the output (action potentials) of BLA projection neurons in response to the stimulus. Neuronal output is controlled by the intrinsic excitability of the neuron. A major determinant of intrinsic excitability in these neurons is the slow afterhyperpolarization (sAHP) that follows action potential (AP) trains and produces spike-frequency adaptation. The sAHP is mediated by a slow calcium-activated potassium current (sI(AHP)), but little is known about the channels that underlie this current. Here, using whole-cell patch-clamp recordings and high-speed calcium imaging from rat BLA projection neurons, we examined the location and function of these channels. We determined the location of the sI(AHP) by applying a hyperpolarizing voltage step during the sI(AHP) and measuring the time needed for the current to adapt to the new command potential, a function of its electrotonic distance from the somatic recording electrode. Channel location was also probed by focally uncaging calcium using a UV laser. Both methodologies indicated that, in BLA neurons, the sI(AHP) is primarily located in the dendritic tree. EPSPs recorded at the soma were smaller, decayed faster, and showed less summation during the sAHP. Adrenergic stimulation and buffering calcium reduced the sAHP and the attenuation of the EPSP during the sAHP. The sAHP also modulated the AP in the dendrite, reducing the calcium response evoked by a single AP. Thus, in addition to mediating spike-frequency adaptation, the sI(AHP) modulates communication between the soma and the dendrite.

Distribution of D1 and D5 dopamine receptors in the primate and rat basolateral amygdala

Dopamine, acting at the D1 family receptors (D1R) is critical for the functioning of the amygdala, including fear conditioning and cue-induced reinstatement of drug self administration. However, little is known about the different contributions of the two D1R subtypes, D(1) and D(5). We identified D(1)-immunoreactive patches in the primate that appear similar to the intercalated cell masses reported in the rodent; however, both receptors were present across the subdivisions of the primate amygdala including the basolateral amygdala (BLA). Using immunoelectron microscopy, we established that both receptors have widespread distributions in BLA. The D1R subtypes colocalize in dendritic spines and terminals, with D(1) predominant in spines and D(5) in terminals. Single-cell RT-PCR confirmed that individual BLA projection neurons express both D(1) and D(5) mRNA. The responses of primate BLA neurons to dopamine and D1R drugs were studied using in vitro slices. We found that responses were similar to those previously reported in rat BLA neurons and included a mixture of postsynaptic and presynaptic actions. We investigated the distribution of D1R in the rat BLA and found that there were similarities between the species, such as more prominent D(5) localization to presynaptic structures. The higher affinity of D(5) for dopamine suggests that presynaptic actions may predominate in the BLA at low levels of dopamine, while postsynaptic effects increase and dominate as dopaminergic drive increases. The results presented here suggest a complex action of dopamine on BLA circuitry that may evolve with different degrees of dopaminergic stimulation.

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.

Identification of a Neuropeptide S Responsive Circuitry Shaping Amygdala Activity via the Endopiriform Nucleus

Neuropeptide S (NPS) and its receptor are thought to define a set of specific brain circuits involved in fear and anxiety. Here we provide evidence for a novel, NPS-responsive circuit that shapes neural activity in the mouse basolateral amygdala (BLA) via the endopiriform nucleus (EPN). Using slice preparations, we demonstrate that NPS directly activates an inward current in 20% of EPN neurons and evokes an increase of glutamatergic excitation in this nucleus. Excitation of the EPN is responsible for a modulation of BLA activity through NPS, characterized by a general increase of GABAergic inhibition and enhancement of spike activity in a subset of BLA projection neurons. Finally, local injection of NPS to the EPN interferes with the expression of contextual, but not auditory cued fear memory. Together, these data suggest the existence of a specific NPS-responsive circuitry between EPN and BLA, likely involved in contextual aspects of fear memory.

Competition between calcium-activated K+ channels determines cholinergic action on firing properties of basolateral amygdala projection neurons.

Acetylcholine (ACh) is an important modulator of learning, memory, and synaptic plasticity in the basolateral amygdala (BLA) and other brain regions. Activation of muscarinic acetylcholine receptors (mAChRs) suppresses a variety of potassium currents, including sI(AHP), the calcium-activated potassium conductance primarily responsible for the slow afterhyperpolarization (AHP) that follows a train of action potentials. Muscarinic stimulation also produces inositol 1,4,5-trisphosphate (IP(3)), releasing calcium from intracellular stores. Here, we show using whole-cell patch-clamp recordings and high-speed fluorescence imaging that focal application of mAChR agonists evokes large rises in cytosolic calcium in the soma and proximal dendrites in rat BLA projection neurons that are often associated with activation of an outward current that hyperpolarizes the cell. This hyperpolarization results from activation of small conductance calcium-activated potassium (SK) channels, secondary to the release of calcium from intracellular stores. Unlike bath application of cholinergic agonists, which always suppressed the AHP, focal application of ACh often evoked a paradoxical enhancement of the AHP and spike-frequency adaptation. This enhancement was correlated with amplification of the action potential-evoked calcium response and resulted from the activation of SK channels. When SK channels were blocked, cholinergic stimulation always reduced the AHP and spike-frequency adaptation. Conversely, suppression of the sI(AHP) by the beta-adrenoreceptor agonist, isoprenaline, potentiated the cholinergic enhancement of the AHP. These results suggest that competition between cholinergic suppression of the sI(AHP) and cholinergic activation of the SK channels shapes the AHP and spike-frequency adaptation.

Group II metabotropic glutamate receptors in anxiety circuitry: Correspondence of physiological response and subcellular distribution

Activation of group II metabotropic glutamate receptors (mGluR2/3) in the amygdala plays a critical role in the regulation of fear and anxiety states. Previous studies using nonselective agonists have suggested this action can result from activation of either pre- or postsynaptic mGluR2/3. Here, we have used a combination of whole-cell patch clamp recording with highly selective agonists (LY354740 and LY379268) and immunoelectron microscopy to examine structure-function relationships for mGluR2/3 in the basolateral amygdala (BLA) and bed nucleus of the stria terminalis (BNST). Stimulation of mGluR2/3 evoked a direct, TTX-insensitive membrane hyperpolarization in all BLA projection neurons tested, but only about half of BNST neurons. The membrane hyperpolarization was mediated by activation of an outward potassium current or blockade of a tonically active inward I(h) current in different groups of BLA neurons. In both regions, mGluR2/3 caused a long-lasting reduction of glutamate release from presynaptic afferent terminals even at concentrations that failed to elicit a direct postsynaptic response. The localization of mGluR2/3 differed regionally, with postsynaptic labeling significantly more common in BLA than BNST, corresponding to the strength of postsynaptic responses recorded there. Our results demonstrate a complex role for mGluR2/3 receptors in modulating anxiety circuitry, including direct inhibition and reduction of excitatory drive. The combination of direct inhibition of projection neurons within the BLA and suppression of excitatory neurotransmission in the BNST may be responsible for the anxiolytic actions of group II mGluR agonists.

Distribution of IP3‐mediated calcium responses and their role in nuclear signalling in rat basolateral amygdala neurons

Metabotropic receptor activation is important for learning, memory and synaptic plasticity in the amygdala and other brain regions. Synaptic stimulation of metabotropic receptors in basolateral amygdala (BLA) projection neurons evokes a focal rise in free Ca(2+) in the dendrites that propagate as waves into the soma and nucleus. These Ca(2+) waves initiate in the proximal dendrites and show limited propagation centrifugally away from the soma. In other cell types, Ca(2+) waves have been shown to be mediated by either metabotropic glutamate receptor (mGluR) or muscarinic receptor (mAChR) activation. Here we show that mGluRs and mAChRs act cooperatively to release Ca(2+) from inositol 1,4,5-trisphosphate (IP(3))-sensitive intracellular Ca(2+) stores. Whereas action potentials (APs) alone were relatively ineffective in raising nuclear Ca(2+), their pairing with metabotropic receptor activation evoked an IP(3)-receptor-mediated Ca(2+)-induced Ca(2+) release, raising nuclear Ca(2+) into the micromolar range. Metabotropic-receptor-mediated Ca(2+)-store release was highly compartmentalized. When coupled with metabotropic receptor stimulation, large robust Ca(2+) rises and AP-induced amplification were observed in the soma, nucleus and sparsely spiny dendritic segments with metabotropic stimulation. In contrast, no significant amplification of the Ca(2+) transient was detected in spine-dense high-order dendritic segments. Ca(2+) rises evoked by photolytic uncaging of IP(3) showed the same distribution, suggesting that IP(3)-sensitive Ca(2+) stores are preferentially located in the soma and proximal dendrites. This distribution of metabotropic-mediated store release suggests that the neuromodulatory role of metabotropic receptor stimulation in BLA-dependent learning may result from enhanced nuclear signalling.

Identification of Basolateral Amygdala Projection Cells and Interneurons Using Extracellular Recordings

This study tested whether firing rate and spike shape could be used to distinguish projection cells from interneurons in extracellular recordings of basolateral amygdala (BLA) neurons. To this end, we recorded BLA neurons in isoflurane-anesthetized animals with tungsten microelectrodes. Projection cells were identified by antidromic activation from cortical projection sites of the BLA. Although most projection cells fired spontaneously at low rates (<1 Hz), an important subset fired at higher rates (up to 6.8 Hz). In fact, the distribution of firing rates in projection cells and unidentified BLA neurons overlapped extensively, even though the latter cell group presumably contains a higher proportion of interneurons. The only difference between the two distributions was a small subset (5.1%) of unidentified neurons with unusually high firing rates (9-16 Hz). Similarly, distributions of spike durations in both cell groups were indistinguishable, although most of the fast-firing neurons had spike durations at the low end of the distribution. However, we observed that spike durations depended on the exact position of the electrode with respect to the recorded cell, varying by as much as 0.7 ms. Thus neither firing rate nor spike waveform allowed for unequivocal separation of projection cells from interneurons. Nevertheless, we propose the use of two firing rate cutoffs to obtain relatively pure samples of projection cells and interneurons: < or =1 Hz for projection cells and > or =7 Hz for fast-spiking interneurons. Supplemented with spike-duration cutoffs of > or =0.7 ms for projection cells and < or =0.5 ms for interneurons, this approach should keep instances of misclassifications to a minimum.

Dopamine D1 receptors co-distribute with N-methyl- d-aspartic acid type-1 subunits and modulate synaptically-evoked N-methyl- d-aspartic acid currents in rat basolateral amygdala

Activation of dopamine D1 or glutamate, N-methyl- d-aspartic acid (NMDA) receptors in the basolateral amygdala (BLA) can potently influence affective behaviors and associative learning. Physical protein–protein interactions also can occur between C-terminal peptides of D1 receptors and the NMDA-receptor subunit-1 (NR1), suggesting intracellular associations of direct relevance to dopaminergic modulation of NMDA currents. We examined this possibility by combining electron microscopic immunolabeling of the D1 and NR1 C-terminal peptides with in vitro patch-clamp recording in the rat BLA. In the in vivo preparations, D1 and NR1 were localized to the surface or endomembranes of many of the same somata and dendrites as well as a few axon terminals, including those forming asymmetric, excitatory-type synapses. In vitro analysis of physiologically characterized projection neurons revealed an excitatory response to bath application of either dopamine or the preferential D1 receptor agonist, dihydrexidine. In these neurons, dopamine also selectively reduced stimulation-evoked isolated NMDA receptor-mediated currents, but not isolated non-NMDA receptor-mediated currents or the response to exogenous NMDA application. The selective reduction of the NMDA receptor-mediated currents suggests that this effect occurs at a postsynaptic locus. Moreover, both D1 and NR1 were localized to postsynaptic surfaces of biocytin-filled and physiologically characterized projection neurons. Our results provide ultrastructural evidence for D1/NR1 endomembrane associations that may dynamically contribute to the attenuation of NMDA receptor-mediated currents following prior activation of D1 receptors in BLA projection neurons. The potential for postsynaptic cross-talk between D1 and NMDA receptors in BLA projection neurons as well as a similar interaction in presynaptic terminals could have important implications for the formation and extinction of affective memories.

Cannabinoids modulate neuronal firing in the rat basolateral amygdala: evidence for CB1- and non-CB1-mediated actions

Recent evidence indicates that the basolateral amygdala (BLA) may be involved in behavioural effects induced by cannabinoids. High levels of CB1 cannabinoid receptors have been shown in this region, where they modulate excitatory and inhibitory synaptic transmission. However, the neurophysiological effects of these opposing synaptic actions have not been investigated in vivo. To this purpose, single-unit extracellular recordings were performed in urethane anaesthetized rats in order to determine whether exogenously applied cannabinoids influenced the spontaneous or evoked electrical activity of neurons in the BLA. The effects of cannabinoids were found to be dependent on the characteristics of the neurons examined and on the properties of the agents used. We tested and compared two structurally different synthetic cannabinoid receptor agonists, the highly potent HU-210 (0.125–1.0 mg/kg, i.v.) and WIN55212-2 (WIN, 0.125–1.0 mg/kg, i.v.). With a CB1 cannabinoid receptor-dependent mechanism, HU-210 potently inhibited the firing rate of BLA interneurons whereas WIN modulated the discharge rate in a biphasic manner. By contrast, BLA projection neurons, antidromically identified from the shell of the nucleus accumbens, were significantly inhibited by WIN at all doses tested, while HU-210 administration led to less consistent effects, since only 1.0 mg/kg inhibited firing rate in the majority of recorded neurons. Additionally, WIN, but not HU-210, significantly attenuated short-latency spiking activity in BLA projection neurons evoked by electrical stimulation of the medial prefrontal cortex. In these neurons, WIN-induced effects were antagonised by the non-selective cannabinoid receptor antagonist SR141716A and by the vanilloid receptor antagonist capsazepine, but not by the selective CB1 antagonist AM-251. Taken together, our findings indicate that the overall excitability of efferent neurons in the BLA is strongly reduced by WIN in a non-CB1-dependent manner. In this effect, the contribution of a novel cannabinoid-vanilloid-sensitive putative non-CB1 receptors, the existence of which was postulated in recent reports, might play a role.

Regulation of conditioned responses of basolateral amygdala neurons

The basolateral amygdala (BLA) is a component of a system that drives and modulates affective behavior. Some forms of affective behavior are regulated by the prefrontal cortex (PFC) and enhanced by dopamine (DA). By using intracellular and extracellular electrophysiological techniques in anesthetized rats, our studies attempt to uncover cellular mechanisms that allow for regulation of affect by PFC-induced inhibition of BLA output and plasticity, as well as mechanisms by which DA enhances affective behavior via modulation of BLA neuronal excitability, afferent input and plasticity. We have found that stimulation of medial PFC (mPFC) results in a profound inhibition of BLA output, manifest as a suppression of spontaneous, intracellular current-driven or sensory cortical afferent-driven spike firing of BLA projection neurons. This inhibition is mediated by excitation of GABAergic interneurons of the BLA. Activation of DA receptors attenuates this inhibitory action of the mPFC, while enhancing other (i.e., sensory-related) inputs by increases in postsynaptic excitability of BLA projection neurons. Furthermore, Pavlovian conditioning procedures that pair an odor with a footshock result in enhanced odor-evoked postsynaptic potentials. This plasticity of odor-evoked responses is blocked by antagonism of DA receptors and by stimulation of mPFC. Our data indicate that the mPFC exerts regulatory control over BLA via suppression of spontaneous and sensory-driven activity, as well as BLA plasticity. Activation of DA receptors suppresses the inhibitory influence of the mPFC, allowing sensory-driven BLA activity and plasticity. Functionally, in the presence of high DA levels, which suppresses mPFC-evoked inhibition, one source of affective control will be dampened. Furthermore, sensory-related inputs will be further enhanced by the increased excitability of BLA neurons. This situation is expected to maximize affective responses to sensory stimuli, as well as plasticity.

Cellular Mechanisms of Infralimbic and Prelimbic Prefrontal Cortical Inhibition and Dopaminergic Modulation of Basolateral Amygdala NeuronsIn Vivo

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.

Modulation of Basolateral Amygdala Neuronal Firing and Afferent Drive by Dopamine Receptor ActivationIn Vivo

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.

Basolateral amygdala stimulation evokes glutamate receptor-dependent dopamine efflux in the nucleus accumbens of the anaesthetized rat.

Afferents from the basolateral amygdala and dopamine projections from the ventral tegmental area to the nucleus accumbens have both been implicated in reward-related processes. The present study used in vivo chronoamperometry with stearate-graphite paste electrodes in urethane-anaesthetized rats to determine how basolateral amygdala efferents to the nucleus accumbens synaptically regulate dopamine efflux. Repetitive-pulse (20 Hz for 10 s) electrical stimulation of the basolateral amygdala evoked a complex pattern of changes in monitored dopamine oxidation currents in the nucleus accumbens related to dopamine efflux. These changes were characterized by an initial increase that was time-locked to stimulation, a secondary decrease below baseline, followed by a prolonged increase in the dopamine signal above baseline. The effects of burst-patterned stimulation (100 Hz, 5 pulses/burst, 1-s interburst interval, 40 s) of the basolateral amygdala on the basal accumbens dopamine signal were similar to those evoked by 20 Hz stimulation, with the lack of a secondary suppressive component. Infusions of the ionotropic glutamate receptor antagonists (+/-)-2-amino-5-phosphonopentanoic acid (APV) or 6,7-dinitroquinoxaline-2,3-dione (DNQX) into the nucleus accumbens dose-dependently blocked or attenuated the initial and prolonged increases in the dopamine signal following 20 Hz or burst-patterned basolateral amygdala stimulation. Infusions of the metabotropic glutamate receptor antagonist (+)-alpha-methyl-4-carboxyphenylglycine selectively blocked the intermediate suppressive effect of 20 Hz basolateral amygdala stimulation on dopamine oxidation currents. Blockade of glutamate receptors or inhibition of dopamine neuronal activity via infusions of either APV + DNQX, lidocaine or gamma-hydroxybutyric acid, respectively, into the ventral tegmental area did not effect the pattern of changes in the accumbens dopamine signal evoked by basolateral amygdala stimulation. These data suggest that the glutamatergic basolateral amygdala inputs to nucleus accumbens dopamine terminals synaptically facilitate or depress dopamine efflux, and these effects are independent of dopamine neuronal firing activity. Moreover, these results imply that changes in nucleus accumbens dopamine levels following presentation of reward-related stimuli may be mediated, in part, by the basolateral amygdala.

Input from the amygdala to the rat nucleus accumbens: Its relationship with tyrosine hydroxylase immunoreactivity and identified neurons

Both tyrosine hydroxylase-positive fibres from the mesolimbic dopamine system and amygdala projection fibres from the basolateral nucleus are known to terminate heavily in the nucleus accumbens. Caudal amygdala fibres travelling dorsally via the stria terminalis project densely to the nucleus accumbens shell, especially in the dopamine rich septal hook. The amygdala has been associated with the recognition of emotionally relevant stimuli while the mesolimbic dopamine system is implicated with reward mechanisms. There is behavioural and electrophysiological evidence that the amygdala input to the nucleus accumbens is modulated by the mesolimbic dopamine input, but it is not known how these pathways interact anatomically within the nucleus accumbens. Using a variety of neuroanatomical techniques including anterograde and retrograde tracing, immunocytochemistry and intracellular filling, we have demonstrated convergence of these inputs on to medium-sized spiny neurons. The terminals of the basolateral amygdala projection make asymmetrical synapses predominantly on the heads of spines which also receive on their necks or adjacent dendrites, symmetrical synaptic input from the mesolimbic dopamine system. Some of these neurons have also been identified as projection neurons, possibly to the ventral pallidum. We have shown a synaptic level how dopamine is positioned to modulate excitatory limbic input in the nucleus accumbens.

The cortical projection of the basolateral amygdaloid nucleus in the rat: a retrograde fluorescent dye study.

The fluorescent dye, retrograde labeling technique was used to determine the extent of the projection from the basolateral nucleus of the amygdala to the neocortex in the rat. Each rat received a single cortical injection of fast blue, and in one-half of the animals, a subsequent injection of nuclear yellow was placed in a different cortical region. An analysis of the results demonstrates that the projection to the midline cortex arises in the medial neurons within the caudal two-thirds of the basolateral nucleus. This projection is directed to the anterior cingulate cortex, but not to the posterior cingulate cortex. The primary motor cortex receives a basolateral amygdala projection which originates from neurons in two areas, (1) the medial part of the anterior one-third of the nucleus and (2) the center (in the lateral to medial axis) portion of the posterior two-thirds of the nucleus. The latter neurons are situated lateral to the neurons projecting to the cingulate cortex. Somatosensory cortex injections label many fewer basolateral nucleus neurons than do motor cortex injections, but these neurons are located in a position similar to that of those labeled by motor cortex injections. Finally the gustatory cortex, which lies just dorsal to the rhinal sulcus, receives a basolateral projection from neurons in the lateroventral one-half of the basolateral nucleus. These results demonstrate that the basolateral nucleus gives rise to a rather widespread and topographically organized projection to the anterior half of the neocortex of the rat.