Sah, P., E. S. L. Faber, M. Lopez de Armentia, and J. Power. The Amygdaloid Complex: Anatomy and Physiology. Physiol Rev 83: 803–834, 2003; 10.1152/physrev.00002.2003.—A converging body of literature over the last 50 years has implicated the amygdala in assigning emotional significance or value to sensory information. In particular, the amygdala has been shown to be an essential component of the circuitry underlying fear-related responses. Disorders in the processing of fear-related information are likely to be the underlying cause of some anxiety disorders in humans such as posttraumatic stress. The amygdaloid complex is a group of more than 10 nuclei that are located in the midtemporal lobe. These nuclei can be distinguished both on cytoarchitectonic and connectional grounds. Anatomical tract tracing studies have shown that these nuclei have extensive intranuclear and internuclear connections. The afferent and efferent connections of the amygdala have also been mapped in detail, showing that the amygdaloid complex has extensive connections with cortical and subcortical regions. Analysis of fear conditioning in rats has suggested that long-term synaptic plasticity of inputs to the amygdala underlies the acquisition and perhaps storage of the fear memory. In agreement with this proposal, synaptic plasticity has been demonstrated at synapses in the amygdala in both in vitro and in vivo studies. In this review, we examine the anatomical and physiological substrates proposed to underlie amygdala function.

BackgroundRecently, we developed a goat model of chronic atrial fibrillation (AF). Due to AF, the atrial effective refractory period (AERP) shortened and its physiological rate adaptation inversed, whereas the rate and stability of AF increased. The goal of the present study was to evaluate the role of (1) the autonomic nervous system, (2) ischemia, (3) stretch, (4) atrial natriuretic factor (ANF), and (5) rapid atrial pacing in this process of electrical remodeling.Methods and ResultsTwenty-five goats were chronically instrumented with multiple epicardial atrial electrodes. Infusion of atropine (1.0 mg/kg; n=6) or propranolol (0.6 mg/kg; n=6) did not abolish the AF-induced shortening of AERP or interval (AFI). Blockade of K⁺_ATPchannels by glibenclamide (10 μmol/kg; n=6) slightly increased the AFI from 95±4 to 101±5 ms, but AFI remained considerably shorter than during acute AF (145 ms). Glibenclamide had no significant effect on AERP after electrical cardioversion of AF (69±14 versus 75±15 ms). Volume loading by 0.5 to 1.0 L of Hemaccel (n=12) did not shorten AERP. The median plasma level of ANF increased from 42 to 99 pg/mL after 1 to 4 weeks of AF (n=6), but ANF infusion (0.1 to 3.1 μg/min, n=4) did not shorten AERP. Rapid atrial pacing (24 to 48 hours; n=10) progressively shortened AERP from 134±10 to 105±6 ms and inversed its physiological rate adaptation.ConclusionsElectrical remodeling by AF is not mediated by changes in autonomic tone, ischemia, stretch, or ANF. The high rate of electrical activation itself provides the stimulus for the AF-induced changes in AERP.

The formation of new synapses has been suggested to underlie learning and memory. However, previous work from this laboratory has demonstrated that hippocampus-dependent associative learning does not induce a net gain in the total number of hippocampal synapses and, hence, a net synaptogenesis. The aim of the present work was to determine whether associative learning involves a specific synaptogenesis confined to the formation of multiple-synapse boutons (MSBs) that synapse with more than one dendritic spine. We used the behavioral paradigm of trace eyeblink conditioning, which is a hippocampus-dependent form of associative learning. Conditioned rabbits were given daily 80-trial sessions to a criterion of 80% conditioned responses in a session. During each trial, the conditioned stimulus (tone) and the unconditioned stimulus (corneal airpuff) were presented with an intervening trace interval of 500 msec. Brain tissue was taken for morphological analyses 24 hr after the last session. Unbiased stereological methods were used for obtaining estimates of the total number of MSBs in the stratum radiatum of hippocampal subfield CA1. The results showed that the total number of MSBs was significantly increased in conditioned rabbits as compared with pseudoconditioned or unstimulated controls. This conditioning-induced change, which occurs without a net synaptogenesis, reflects a specific synaptogenesis resulting in MSB formation. Models of the latter process are proposed. The models postulate that it requires spine motility and may involve the relocation of existing spines from nonactivated boutons or the outgrowth of newly formed spines for specific synaptogenesis with single-synapse boutons activated by the conditioning stimulation.

Classical conditioning paradigms, such as trace conditioning, in which a silent period elapses between the offset of the conditioned stimulus (CS) and the delivery of the unconditioned stimulus (US), and delay conditioning, in which the CS and US coterminate, are widely used to study the neural substrates of associative learning. However, there are significant gaps in our knowledge of the neural systems underlying conditioning in humans. For example, evidence from animal and human patient research suggests that the hippocampus plays a critical role during trace eyeblink conditioning, but there is no evidence to date in humans that the hippocampus is active during trace eyeblink conditioning or is differentially responsive to delay and trace paradigms. The present work provides a direct comparison of the neural correlates of human delay and trace eyeblink conditioning by using functional MRI. Behavioral results showed that humans can learn both delay and trace conditioning in parallel. Comparable delay and trace activation was measured in the cerebellum, whereas greater hippocampal activity was detected during trace compared with delay conditioning. These findings further support the position that the cerebellum is involved in both delay and trace eyeblink conditioning whereas the hippocampus is critical for trace eyeblink conditioning. These results also suggest that the neural circuitry supporting delay and trace eyeblink classical conditioning in humans and laboratory animals may be functionally similar.

Aging is associated with learning deficits and a decrease in neuronal excitability, reflected by an enhanced post-burst afterhyperpolarization (AHP), in CA1 hippocampal pyramidal neurons. To identify the current(s) underlying the AHP altered in aging neurons, whole-cell voltage-clamp recording experiments were performed in hippocampal slices from young and aging rabbits. Similar to previous reports, aging neurons were found to rest at more hyperpolarized potentials and have larger AHPs than young neurons. Given that compounds that reduce the slow outward calcium-activated potassium current (sI_AHP), a major constituent of the AHP, also facilitate learning in aging animals, the sI_AHP was pharmacologically isolated and characterized. Aging neurons were found to have an enhanced sI_AHP, the amplitude of which was significantly correlated to the amplitude of the AHP (r = 0.63; p < 0.001). Thus, an enhanced sI_AHP contributes to the enhanced AHP in aging. No differences were found in the membrane resistance, capacitance, or kinetic and voltage-dependent properties of the sI_AHP. Because enhanced AHP in aging neurons has been hypothesized to be secondary to an enhanced Ca²⁺ influx via the voltage-gated L-type Ca²⁺ channels, we further examined the sI_AHP in the presence of an L-type Ca²⁺ channel blocker, nimodipine (10 μm). Nimodipine caused quantitatively greater reductions in the sI_AHP in aging neurons than in young neurons; however, the residual sI_AHP was still significantly larger in aging neurons than in young neurons. Our data, in conjunction with previous studies showing a correlation between the AHP and learning, suggest that the enhancement of the sI_AHP in aging is a mechanism that contributes to age-related learning deficits.