The morphology of neurons in the central nucleus has been studiedusing Golgi techniques as well as reconstruction after recordingphysiological properties in acute brain slices (144, 252).As with the basolateral complex, the different subdivisionsof the central nucleus (30, 105, 149, 208) cannot be easilyidentified in acute slices maintained in vitro (Fig. 5). Thus,while Golgi studies have described neurons in the differentsubdivisions, results from cell fills in slices have eithernot discussed subdivisions (252) or divided cells into thosein the lateral and medial sectors (144, 251). Here we willtherefore concentrate on cells in the lateral and medial sectorsof the central nucleus. There is general agreement that inboth subdivisions there is one predominant cell type that hasbeen called "medium spiny neurons" in the CeL by comparisonwith neurons in the nearby striatum (73, 149). These cellshave an ovoid or fusiform soma and three to five nonspiny primarydendrites from which moderately spiny, sparsely branching secondaryand tertiary dendrites arise (144, 149, 252). Axons giveoff several local collaterals before leaving the nucleus. Asecond type of neuron has also been described that has a somewhatlarger soma and a thick primary aspiny dendrite that tapersinto sparsely spiny secondary dendrites (29, 149, 252). Inaddition, a small number of aspiny neurons have also been described(29). These three cell types are distributed homogeneouslythroughout the CeA. Immunohistochemical studies have demonstratedthe presence of a wide variety of peptides in cells in the CeA as well as in the afferents innervating these neurons (29,30, 177). One study has shown that the peptides enkephalin,neurotensin and corticotropin releasing hormone (CRH) is foundin GABAergic neurons. There appear to be two populations ofthese cells: one contains enkephalin and the other CRH (44).Both populations have a partial overlap with neurotensin containingneurons (44, 258). Interestingly, intraperitoneal administrationof the cytokine interleukin-1 preferentially activated GABAergicneurons containing enkephalin (44), suggesting that neuronswith different peptide content have different functional roles.Thus neurons in the central nucleus are morphologically verydifferent from those found in the basolateral complex withbasolateral neurons having similar morphology to cortical structuresand the central nucleus being more striatal-like (73, 149).This finding is consistent with the different embryologicalorigins of the two nuclei (214, 269). Finally, as with themajority of cells in the striatum, projections from the centralnuclei are predominantly GABAergic while the basolateral nucleihave glutamatergic projections (42, 244, 269).
B. Physiological Properties
Only a small number of studies have examined the electrophysiologicalproperties of cells in the central nucleus (144, 190, 251,252). These recordings have been performed in vitro in coronalslices from rat and guinea pig using either whole cell or microelectroderecordings. As discussed above, cells have only been describedin the lateral and medial subdivisions as the boundaries forthe intermediate and capsular divisions are not apparent inacute slices. At least three types of cells have been describedthat can be separated by their firing properties (Fig. 9).Using intracellular recordings with sharp microelectrodes,Schiess and co-workers (251, 252) described two types of cells that they called type A and B cells. Type A (75%) cellsfired throughout a prolonged current injection, showing littlespike frequency adaptation, and action potentials were followedby a medium-duration AHP (243) in response to short depolarizingcurrent injections. Type B cells (25%) accommodated and exhibitedboth a medium and slow AHP. The two cell types had similar passivemembrane properties other than the resting membrane potential,which was more depolarized in type B cells. Using whole cellrecordings in guinea pig slices in vitro, Martina et al. (144)divided cells into three types. The most common type was describedas "late firing" (95% in CeM and 56% in CeL; Fig. 9C). Thesecells displayed a pronounced outward rectification in the depolarizingdirection (144). In addition to the late-firing neurons, theCeL also contained neurons that fired spikes repetitively inresponse to a prolonged current injection and were termed "regularspiking" cells (40%, Fig. 9B). The regular firing cells ofMartina et al. (144) likely correspond to type A cells describedin the rat (251).
Two further cell types were described in the guinea pig thatwere called fast-spiking cells and "burst-firing" cells (144).Fast-spiking cells were typical of interneurons and fired fastaction potentials at high frequency, showing no accommodation.In contrast, burst-firing cells fired repetitively, showingsome accommodation, in response to a prolonged current injectionand fired rebound bursts of action potentials, riding on a depolarizing potential (Fig. 9A). These cells therefore aresimilar to the type B cells described in the rat (251). However,after a hyperpolarizing current step, low-threshold burstingneurons in the guinea pig show a clear rebound depolarization,similar to that reported by Scheiss et al. (251) in type Acells. It should be noted that the whole cell recordings ofMartina et al. (144) were made with potassium gluconate-containinginternal solutions, which makes comparison with microelectroderecordings difficult since the slow AHP is very sensitive tothe anion present in the internal solution (299). Thus someof the discrepancies in the findings of Schiess and co-workers(251, 252) and Martina et al. (144) may be due to the differentrecording techniques used. In addition, it is notable that thesestudies were done in different species, and it has recentlybeen suggested that there are differences in the distributionof cells with distinct properties between rat, cat, and guineapig (50). Thus, for example, while late-firing neurons constituted>90% of the cell population in the CeM in guinea pigs, theyaccounted for only 2 and 6% of neurons in the rat and cat CeM,respectively (50).
After recovery of physiologically identified neurons, cellsin the CeL were found to have generally smaller cell bodiesthan cells in the CeM (144). However, while in the rat Scheisset al. (251) suggested that the two cells types they foundhad different cell morphologies, Martina et al. (144) did notfind any systematic correlation between cell firing propertiesand their morphology. In both studies, the major physiologicalcell type recovered corresponded to the medium spiny neuronsdescribed in Golgi studies.
C. Synaptic Properties
Consistent with tract tracing studies, experiments in acuteslices from rats and guinea pig have shown that neurons inboth the CeM and CeL receive glutamatergic inputs from thelateral and basal nucleus which activate both AMPA and NMDAreceptors (130, 239). In the guinea pig, CeL neurons largelyreceive inputs from the lateral nucleus while neurons in themedial subdivision receive inputs from the basal nucleus (239).It should be noted, however, that when recording from CeL neuronsin acute brain slices, cells are difficult to separate fromthose in the capsular subdivision unless they are filled, recovered,and divisional boundaries visualized histologically.
Excitatory inputs to CeL neurons also express presynaptic metabotropicglutamate receptors (186). As in many other regions of thecentral nervous system (132, 207), activation of these receptorsleads to depression of the synaptic input. The activity of thesereceptors is modulated following kindling and chronic cocainetreatment (186). The central amygdala is particularly sensitiveto a kindling stimulus (123a) and has been implicated in thereinforcing ability of repeated cocaine exposure (170). Thesefindings suggest that alterations in synaptic efficacy at inputsto the CeA may be involved in the changes seen in epilepsyand behavioral sensitization to cocaine.
In the lateral subdivision of the central nucleus, two distincttypes of ionotropic GABA receptors have been demonstrated.One type is similar to typical GABAA receptors and is blockedby low concentrations of bicuculline and positively modulatedby benzodiazepines and barbiturates (293). In addition, thesecells express a second type of GABA receptor that is markedlyless sensitive to bicuculline. This bicuculline-resistant componentwas initially suggested to be due to activation of nicotinicacetylcholine receptors (190). However, recent experimentshave shown that it is blocked by the specific GABAC receptorantagonist 1,2,5,6-tetrahydropyridine-(4-yl)methylphosphinicacid (TPMPA) (46). These receptors have been called GABAC-likereceptors due to their pharmacological similarity to retinalGABAC receptors (89, 217). Bicuculline-insensitive receptorshave also been shown to be present in the medial subdivision(239), indicating these receptors are present throughout thecentral nucleus. Although bicuculline-insensitive ionotropicGABA receptors have been described in other regions of thecentral nervous system (90), the presence of these receptorsat synapses has not been shown outside the central amygdala.The two GABA receptor types appear to be localized to differentGABAergic inputs onto CeL neurons. Thus inputs from the intercalatedneurons that form synapses onto the dendrites of CeL neuronsexpress both GABAA- and GABAC-like receptors. In contrast,a different input that enters the central nucleus from a dorsomedialsource activates synapses located on the soma. These somaticsynapses express only GABAA receptors (47). The initial segmentof CeL neuron axons is spiny (149). It is therefore temptingto speculate that if the somatic GABAergic synapses were madeonto these spines, their activity would constitute a powerfulmeans to inhibit the output of CeL neurons. These results suggestthat the different GABA receptors may play distinct roles inthe local circuitry of the central amygdala (47). Interestingly,the GABAC-like receptor is negatively modulated by benzodiazepinessuch as diazepam (47). The amygdaloid complex has long beenknown to have a high density of benzodiazepine binding sites(188), and the actions of these agents may reflect their actionat sites in the amygdala. Benzodiazepines are thought to producetheir anxiolytic actions by enhancing the activity of GABAAreceptor-mediated inhibitory synaptic potentials (192). Thepresence of a GABA receptor in the central amygdala with anovel benzodiazepine pharmacology suggests an alternative mechanismfor the anxiolytic actions of benzodiazepines.
The subdivisions of the central nucleus have extensive intradivisionalconnections (see above) (92). Many of the neurons in the centralnuclei are thought to be GABAergic (160, 189, 209). Bothmorphological (265) and electrophysiological (190) studieshave indicated the presence of abundant local GABAergic connectionswithin the central nucleus. However, direct functional evidencefor this is not currently available.