Search

Adverse stress effects on the hippocampal memory system are generally thought to be due to the high level of circulating glucocorticoids directly modifying the properties of hippocampal neurons and, accordingly, the results should be reproducible with exogenous administration of cortisol in humans and corticosterone in rodents. However, glucocorticoid levels increased to other events, such as exercise and environment enrichment, do not impair but instead enhance hippocampal memory, indicating that cortisol/corticosterone are not invariant causal factors of stress. To better model the complex psychophysiological attributes of stress (i.e., aversiveness, lack of controllability, and glucose metabolism), we examined the functions of the amygdala, medial prefrontal cortex (mPFC), and corticosterone on a hippocampal-based one-trial novel object recognition (OR) memory task in rats. Specifically, animals were subjected to amygdala stimulation, mPFC inactivation, and corticosterone treatments separately or in combination during behavioral testing. Collective amygdala, mPFC, and corticosterone manipulations significantly impaired OR memory comparable to behavioral stress. By contrast, single and dual treatments failed to reliably decrease memory functioning. These results suggest that negative mnemonic impacts of uncontrollable stress involve the amalgamation of heightened amygdala and diminished mPFC activities, and elevated circulating corticosterone level. [ABSTRACT FROM AUTHOR]

The periaqueductal gray (PAG) and amygdala are known to be important for defensive responses, and many contemporary fear-conditioning models present the PAG as downstream of the amygdala, directing the appropriate behavior (i.e., freezing or fleeing). However, empirical studies of this circuitry are inconsistent and warrant further examination. Hence, the present study investigated the functional relationship between the PAG and amygdala in two different settings, fear conditioning and naturalistic foraging, in rats. In fear conditioning, electrical stimulation of the dorsal PAG (dPAG) produced unconditional responses (URs) composed of brief activity bursts followed by freezing and 22-kHz ultrasonic vocalization. In contrast, stimulation of ventral PAG and the basolateral amygdalar complex (BLA) evoked freezing and/or ultrasonic vocalization. Whereas dPAG stimulation served as an effective unconditional stimulus for fear conditioning to tone and context conditional stimuli, neither ventral PAG nor BLA stimulation supported fear conditioning. The conditioning effect of dPAG, however, was abolished by inactivation of the BLA. In a foraging task, dPAG and BLA stimulation evoked only fleeing toward the nest. Amygdalar lesion/inactivation blocked the UR of dPAG stimulation, but dPAG lesions did not block the UR of BLA stimulation. Furthermore, in vivo recordings demonstrated that electrical priming of the dPAG can modulate plasticity of subiculum-BLA synapses, providing additional evidence that the amygdala is downstream of the dPAG. These results suggest that the dPAG conveys unconditional stimulus information to the BLA, which directs both innate and learned fear responses, and that brain stimulation-evoked behaviors are modulated by context. [ABSTRACT FROM AUTHOR]

In a natural environment foragers constantly face the risk of encountering predators. Fear is a defensive mechanism evolved to protect animals from danger by balancing the animals' needs for primary resources with the risk of predation, and the amygdala is implicated in mediating fear responses. However, the functions of fear and amygdala in foraging behavior are not well characterized because of the technical difficulty in quantifying prey-predator interaction with real (unpredictable) predators. Thus, the present study investigated the rat's foraging behavior in a seminaturalistic environment when confronted with a predator-like robot programmed to surgetoward the animal seeking food. Rats initially fled into the nest and froze (demonstrating fear) and then cautiously approached and seized the food as a function of decreasing nest-food and increasing food-robot distances. The likelihood of procuring food increased and decreased via lesioning/inactivating and disinhibiting the amygdala, respectively. These results indicate that the amygdala bidirectionally regulates risk behavior in rats foraging in a dynamic fear environment. [ABSTRACT FROM AUTHOR]

It is now well documented that both increased and decreased stress responses can profoundly affect cognition and behavior. This mini review presents possible neural mechanisms subserving stress effects on memory and aggression, particularly focusing on glucocorticoid (GC) hyper- and hypofunction. First, uncontrollable stress impedes hippocampal memory and long-term potentiation (LTP). Because the hippocampus is important for the stability of long-term memory and because LTP has qualities desirable of an information storage mechanism, it has been hypothesized that stress-induced alterations in LTP contribute to memory impairments. Recent evidence suggests a neural–endocrine network comprising amygdala, prefrontal cortex (PFC), and glucocorticoids may be involved in regulating stress effects on hippocampal mnemonic functioning. Second, antisocial aggressiveness correlates with chronically decreased glucocorticoid production, and this condition leads in rats to behavioral–autonomic deficits reminiscent of the human disorder. Glucocorticoid deficiency-induced antisocial aggressiveness results from functional changes in the PFC, medial and central amygdala, and altered serotonin and substance P neurotransmissions. Accordingly, a neurobiological understanding of how stress and glucocorticoid deficiency alter brain, cognition, and behavior is an important challenge facing modern neuroscience with broad implications for individual and social well-being. [ABSTRACT FROM AUTHOR]

The neural substrates of fear conditioning in rats have been well characterized, with converging lines of evidence indicating that conditioned stimulus (CS) and unconditioned stimulus (US) information form a CS–US association in the amygdala. Auditory CS information can reach the amygdala via two routes: a direct thalamo-amygdala pathway, and an indirect thalamo-cortico-amygdala pathway. Although either pathway can fully support learning when the alternate pathway is disrupted, many studies to date have argued that the thalamo-amygdala pathway is the principal auditory CS pathway in intact brains. To test this hypothesis, we trained rats in auditory fear conditioning, and 24 h later lesioned either pathway, leaving the alternate pathway intact. Later, animals were tested for conditioned freezing to the auditory CS. We report that lesions of the thalamo-amygdala pathway produced severe but incomplete deficits in freezing during the tone retention test, while lesions of the thalamo-cortico-amygdala pathway completely abolished freezing during tone presentation. These results suggest that the thalamo-cortico-amygdala pathway is the principal auditory CS pathway when the brain is intact. [ABSTRACT FROM AUTHOR]

Electrolytic lesions to the amygdala, a limbic structure implicated in stress-related behaviors and memory modulation, have been shown to prevent stress-induced impairments of hippocampal long-term potentiation (LTP) and spatial memory in rats. The present study investigated the role of intrinsic amygdalar neurons in mediating stress effects on the hippocampus by microinfusing the GABAA receptor agonist muscimol into the amygdala and examining stress effects on Schaffer collateral/commissural-CA1 LTP and spatial memory. The critical period of the amygdalar contribution to stress effects on hippocampal functions was determined by applying muscimol either before stress or immediately after stress. Our results indicate that intra-amygdalar muscimol infusions before uncontrollable restraint-tailshock stress effectively blocked stress-induced physiological and behavioral effects. Specifically, hippocampal slices prepared from vehicle-infused stressed animals exhibited markedly impaired LTP, whereas slices obtained from muscimol-infused stressed animals demonstrated robust LTP comparable with that of unstressed animals. Correspondingly, vehicle-infused stressed animals displayed impaired spatial memory (on a hidden platform version of the Morris water maze task), whereas muscimol-infused stressed animals revealed unimpaired spatial memory. In contrast to prestress muscimol effects, however, immediate poststress infusions of muscimol into the amygdala failed to interfere with stress impairments of LTP and spatial memory. Together, these results suggest that the amygdalar neuronal activity during stress, but not shortly after stress, is essential for the emergence of stress-induced alterations in hippocampal LTP and memory. [ABSTRACT FROM AUTHOR]

In the fear conditioning literature, it is generally hypothesized that neurons in the basolateral amygdalar complex (BLA) (lateral and basal nuclei) support the formation of conditioned fear memory and project to neurons in the central nucleus (CeA) for the expression of conditioned fear responses. According to this serial processing-transmission view, damage to either BLA or CeA would comparably disrupt the expression of a variety of conditioned fear responses. In the present study, we further investigated the roles of BLA and CeA in fear conditioning by concurrently assessing freezing and 22 kHz ultrasonic vocalization (USV) as dependent measures of fear in rats. Selective neurotoxins, NMDA for the BLA and ibotenic acid for the CeA, were used to destroy intrinsic neurons [evidenced by thionin dye and NeuN (neuronal nuclei) antibody stainings] without damaging the fibers of passage (confirmed by myelin staining). During the 10 tone-footshock paired training, postshock freezing and USV responses were significantly impaired in BLA-lesioned animals, whereas CeA-lesioned animals exhibited only mild deficits. Similarly, conditioned fear responses assessed 24 hr after training were severely reduced in BLA-lesioned animals but not in CeA-lesioned animals. In contrast to ibotenic lesions of the CeA, small electrolytic lesions of the CeA strongly affected both postshock and conditioned freezing and USV. Together, these results do not support the currently espoused BLA-to-CeA serial processing-transmission view of fear conditioning. Instead, the expression of conditioned fear appears to primarily involve BLA projections that course through the CeA en route to downstream fear response structures. [ABSTRACT FROM AUTHOR]

Eyeblink conditioning has been hypothesized to engage two successive stages of nonspecific emotional (fear) and specific musculature (eyelid) learning, during which the nonspecific component influences the acquisition of the specific component. Here we test this notion by investigating the relative contributions of the cerebellum, the amygdala, and the hippocampus to the emergence of conditioned eyelid and fear responses during delay eyeblink conditioning in freely moving rats. Periorbital electromyography (EMG) and 22 kHz ultrasonic vocalization (USV) activities were measured concurrently from the same subjects and served as indices of conditioned eyeblink and fear responses, respectively. In control animals, conditioned EMG responses increased across training sessions, whereas USV responses were initially robust but decreased across training sessions. Animals with electrolytic lesions to their cerebellum (targeting the interpositus nucleus) were completely unable to acquire conditioned EMG responses but exhibited normal USV behavior, whereas animals with lesions to the amygdala showed decelerated acquisition of conditioned EMG responses and displayed practically no USV behavior. In contrast, hippocampal lesioned rats demonstrated facilitated acquisition of conditioned EMG responses, whereas the USV behavior was unaffected. The amygdalar involvement in eyeblink conditioning was examined further by applying the GABAA agonist muscimol directly into the amygdala either before or immediately after training sessions. Although pretraining muscimol infusions impaired conditioned EMG responses, post-training infusions did not. Together, these results suggest that, even during a simple delay eyeblink conditioning, animals learn about different aspects associated with the behavioral task that are subserved by multiple brain-memory systems that interact to produce the overall behavior. [ABSTRACT FROM AUTHOR]

The relative contribution of left and right amygdalae in the acquisition and retention of fear conditioning was investigated in rats. Pretraining bilateral electrolytic lesions blocked the acquisition of conditioned fear to tone and context, whereas unilateral lesions induced partial impairments with no left-right amygdala differences. In contrast, posttraining bilateral and unilateral lesions produced significant deficits in the retention of conditioned fear to tone and context. Although no left-right difference was observed to tone, the right amygdala lesions generated greater deficits in contextual fear than the left amygdala lesions. These results indicate that fear conditioning is partially disrupted with unilateral amygdalar lesions, but that the right amygdala has greater involvement than the left amygdala when conditioning occurs under a normal brain state. [ABSTRACT FROM AUTHOR]

Examines whether the combined posterior extension of the intralaminar complex (PINT) and caudal insular cortex (INS) lesions in the amygdala block fear conditioning as measured by defensive freezing. Involvement of the PINT-INS in unconditioned stimulus information transmission; Effect of the PINT-INS inputs to the amygdala; Reconstructions of the electrolytic lesions of INS and PINT.

Examines the effects of amygdala, hippocampus, and periaqueductal gray (PAG) lesions on contextual fear conditioning in rats. Freezing behavior as a measure of conditioning; N-methyl-D-aspartate receptors (NMDA); Conditional fear to the contextual cues of the chamber.

Reports that the acquisition of contextual Pavlovian fear conditioning is blocked by application of an N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV) to the basolateral amygdala in rats. Administration of APV to the basolateral nucleus; Effect of central nucleus infusions.

Considerable evidence seems to show that emotional and reflex reactions to feared situations are mediated by the amygdala. It might therefore seem plausible to expect that amygdala-coded fear should also influence decisions when animals make choices about instrumental actions. However, there is not good evidence of this. In particular, it appears, though the literature is conflicted, that once learning is complete, the amygdala may often not be involved in instrumental avoidance behaviours. It is therefore of interest that we have found in rats living for extended periods in a semi-naturalistic 'closed economy', where they were given random shocks in regions that had to be entered to obtain food, choices about feeding behaviour were in fact influenced by amygdala-coded fear, in spite of the null effect of amygdalar lesions on fear of dangerous location per se. We suggest that avoidance of highly motivated voluntary behaviour does depend in part on fear signals originating in the amygdala. Such signalling may be one role of well-known projections from amygdala to cortico-striate circuitry. [ABSTRACT FROM AUTHOR]

The article focuses on a study regarding dynamic coding of predatory information between the prelimbic cortex and lateral amygdala in foraging rats. Topics discussed include recording of lateral amygdala (LA) and prelimbic (PL) area neuronal activities as rats exited a safe nest, behaviors of animals and humans against predation and other ecological risks and cell pairs and heterogeneous responses to predatory threat.