Many associative learning theories assert that the predictive accuracy of events affects the allocation of attention to them. More reliable predictors of future events are usually more likely to control action based on past learning, but less reliable predictors are often more likely to capture attention when new information is acquired. Previous studies showed that a circuit including the amygdala central nucleus (CEA) and the cholinergic substantia innominata/nucleus basalis magnocellularis (SI/nBM) is important for both sustained attention guiding action in a five-choice serial reaction time (5CSRT) task and for enhanced new learning about less predictive cues in a serial conditioning task. In this study, the authors found that lesions of the cholinergic afferents of the medial prefrontal cortex interfered with 5CSRT performance but not with surprise-induced enhancement of learning, whereas lesions of cholinergic afferents of posterior parietal cortex impaired the latter effects but did not affect 5CSRT performance. CEA lesions impaired performance in both tasks. These results are consistent with the view that CEA affects these distinct aspects of attention by influencing the activity of separate, specialized cortical regions via modulation of SI/nBM.

Through associative learning, cues for biologically significant reinforcers such as food may gain access to mental representations of those reinforcers. Here, we used devaluation procedures, behavioral assessment of hedonic taste-reactivity responses, and measurement of immediate-early gene (IEG) expression to show that a cue for food engages behavior and brain activity related to sensory and hedonic processing of that food. Rats first received a tone paired with intraoral infusion of sucrose. Then, in the absence of the tone, the value of sucrose was reduced (Devalue group) by pairing sucrose with lithium chloride (LiCl), or maintained (Maintain group) by presenting sucrose and LiCl unpaired. Finally, taste-reactivity responses to the tone were assessed in the absence of sucrose. Devalue rats showed high levels of aversive responses and minimal appetitive responses, whereas Maintain rats exhibited substantial appetitive responding but little aversive responding. Control rats that had not received tone-sucrose pairings did not display either class of behaviors. Devalue rats showed greater FOS expression than Maintain rats in several brain regions implicated in devaluation task performance and the display of aversive responses, including the basolateral amygdala, orbitofrontal cortex, gustatory cortex (GC), and the posterior accumbens shell (ACBs), whereas the opposite pattern was found in the anterior ACBs. Both Devalue and Maintain rats showed greater FOS expression than control rats in amygdala central nucleus, GC, and both subregions of ACBs. Thus, through associative learning, auditory cues for food gained access to neural processing in several brain regions importantly involved in the processing of taste memory information.Reinforcer devaluation procedures are often used to assess cues' ability to guide behavior based on their access to a representation of the current incentive value of the reinforcer. For example, after tone-food pairings, the establishment of an aversion to the food reinforcer results in the spontaneous reduction of rats' learned food-cup approach responses to the tone, when it is presented later in the absence of food (Holland and Straub 1979). Thus, the rats' response to the tone is sensitive to changes in reinforcer value, despite no explicit experience of the tone together with the devalued reinforcer. Recent studies (for review, see Holland and Gallagher 2004) showed that this sensitivity of previously learned behaviors to subsequent alterations in reinforcer value demands function of a brain system that includes the basolateral amygdala (BLA) and the lateral orbitofrontal cortex (OFC).Previous devaluation studies examined changes in performance of learned responses preparatory to the receipt of food, such as food-cup approach. Here, we considered whether a learned cue for food would provoke consummatory responses that reflect the current sensory-hedonic aspects of food. In the absence of food itself, would a food cue provoke "liking" or "disgust" responses appropriate to the current...

When exposed to pairings of a visual stimulus with food delivery, rats normally acquire both conditioned orienting responses directed toward the visual stimulus and conditioned food-related responses. Consistent with the results of previous lesion studies, reversible inactivation of amygdala central nucleus function before each conditioning session prevented the acquisition of conditioned orienting responses, whereas food-related behaviors were acquired normally. By contrast, neither inactivation nor neurotoxic lesions of central nucleus affected the expression of previously acquired conditioned orienting responses. Thus, the central nucleus is apparently not critical to the maintenance of information required for conditioned orienting, but instead is necessary for memory storage elsewhere. Specialized roles for components of a circuit for conditioned orienting, which includes the central nucleus, the substantia nigra, and dorsolateral striatum, are discussed.

Cocaine stimuli often trigger relapse of drug-taking, even following periods of prolonged abstinence. Here, electrophysiological recordings were made in rats (n = 29) to determine how neurons in the prelimbic (PrL) or infralimbic (IL) regions of the medial prefrontal cortex (mPFC) encode cocaine-associated stimuli and cocaine-seeking, and whether this processing is differentially altered after 1 month of cocaine abstinence. After self-administration training, neurons (n=308) in the mPFC were recorded during a single test session conducted either the next day or 1 month later. Test sessions consisted of three phases during which (i) the tone–houselight stimulus previously paired with cocaine infusion during self-administration was randomly presented by the experimenter, (ii) rats responded on the lever previously associated with cocaine during extinction and (iii) the tone–houselight was presented randomly between cocaine-reinforced responding during resumption of cocaine self-administration. PrL neurons showed enhanced encoding of the cocaine stimulus and drug-seeking behavior (under extinction and self-administration) following 30 days of abstinence. In contrast, although IL neurons encoded cocaine cues and cocaine-seeking, there were no pronounced changes in IL responsiveness following 30 days’ abstinence. Importantly, cue-related changes do not represent a generalized stimulus-evoked discharge as PrL and IL neurons in control animals (n=4) exhibited negligible recruitment by the tone–houselight stimulus. The results support the view that, following abstinence, neural encoding in the PrL but not IL may play a key role in enhanced cocaine-seeking, particularly following re-exposure to cocaine-associated cues.

When exposed to pairings of a visual stimulus with food delivery, rats normally acquire both conditioned orienting responses directed toward the visual stimulus and conditioned food-related responses. Consistent with the results of previous lesion studies, reversible inactivation of amygdala central nucleus function before each conditioning session prevented the acquisition of conditioned orienting responses, whereas food-related behaviors were acquired normally. By contrast, neither inactivation nor neurotoxic lesions of central nucleus affected the expression of previously-acquired conditioned orienting responses. Thus, the central nucleus is apparently not critical to the maintenance of information required for conditioned orienting, but instead is necessary for memory storage elsewhere. Specialized roles for components of a circuit for conditioned orienting, which includes the central nucleus, the substantia nigra, and dorsolateral striatum, are discussed.

The shell division of the nucleus accumbens receives noradrenergic input from neurons in the nucleus of the solitary tract (NTS) that transmit information regarding fluctuations in peripheral hormonal and autonomic activity. Accumbens shell neurons also receive converging inputs from limbic areas such as the hippocampus and amygdala that process newly acquired information. However, few studies have explored whether peripheral information regarding changes in emotional arousal contributes to memory processing in the accumbens. The beneficial effects on memory produced by emotional arousal and the corresponding activation of NTS neurons may be mediated through influences on neuronal activity in the accumbens shell during memory encoding. To explore this putative relationship, Experiment 1 examined interactions between the NTS and the accumbens shell in modulating memory for responses acquired after footshock training in a water-motivated inhibitory avoidance task. Memory for the noxious shock was significantly improved by posttraining excitation of noradrenergic NTS neurons. The enhanced retention produced by activating NTS neurons was attenuated by suppressing neuronal activity in the accumbens shell with bupivacaine (0.25%/0.5μl). Experiment 2 examined the direct involvement of accumbens shell noradrenergic activation in the modulation of memory for psychologically arousing events such as a reduction in perceived reward value. Noradrenergic activation of the accumbens shell with phenylephrine (1.0μg/0.5μl) produced an enhancement in memory for the frustrating experience relative to control injections as evidenced by runway performance on an extended seven-day retention test. These findings demonstrate a functional relationship between NTS neurons and the accumbens shell in modulating memory following physiological arousal and identifies a role of norepinephrine in modulating synaptic activity in the accumbens shell to facilitate this process.

The nucleus accumbens shell (NAC) receives axons containing dopamine-b-hydroxylase that originate from brainstem neurons in the nucleus of the solitary tract (NTS). Recent findings show that memory enhancement produced by stimulating NTS neurons after learning may involve interactions with the NAC. However, it is unclear whether these mnemonic effects are mediated by norepinephrine (NE) release from NTS terminals onto NAC neurons. The present studies approached this question by examining the contribution of NAC a-noradrenergic receptors in mediating this effect and assessed whether glutamatergic activation of the NTS alters NE concentrations in the NAC. Rats were trained for 6 d to drink from a water spout located at the end of an inhibitory avoidance chamber. On day 7, a 0.35-mA footshock was initiated once the rat approached the spout and remained active until it escaped into the neutral compartment. Blockade of a-noradrenergic receptors in the NAC with phentolamine (0.5 mg/0.5 mL) attenuated memory enhancement produced by glutamatergic (50 ng/0.5 mL) infusion on NTS neurons (P , 0.01). Experiment 2 used in vivo microdialysis to assess whether glutamate activation of NTS alters NAC NE concentrations. NE levels were unchanged by NTS infusion of phosphate-buffered saline (PBS) or low dose glutamate (50 ng/0.5 mL) but elevated significantly (P , 0.05) by combining the same dose with the footshock (0.35 mA, 2 sec) given in Study 1 or infusion of (100 ng/0.5 mL) glutamate alone. Findings demonstrate that NE released from NTS terminals enhances representations in memory by acting on a-noradrenergic receptors within the NAC.The shell division of the nucleus accumbens (NAC) receives highly processed information regarding affective and contextual features of new learning experiences from the amygdala and hippocampus, respectively (Mogenson et al. 1980;Groenewegen et al. 1987;Meredith et al. 1990;Wang et al. 1992;Brog et al. 1993;Petrovich et al. 1996;French and Totterdell 2003). These limbic inputs are complemented by norepinephrine containing axons supplied by the A2 class of noradrenergic neurons housed in the brainstem region of the nucleus of the solitary tract (NTS) (Delfs et al. 1998). Norepinephrine release from A2 NTS neurons play an important role in conveying information regarding experience-induced changes in the physiological state of the organism.The A2 neurons are activated during times of heightened arousal by the release of glutamate from vagal nerve fibers that ascend from the periphery to the brainstem (Allchin et al. 1994;King and Williams 2009). Highly arousing events increase epinephrine secretion from the adrenals and facilitate binding to b-adrenergic receptors along the vagus nerve (Lawrence et al. 1995) that in turn, increase impulse flow to brainstem neurons in the NTS (Lawrence et al. 1995;Miyashita and Williams 2006). Epinephrine administration, stimulation of the vagus nerve or direct infusion of glutamate onto A2 NTS neurons are all known to significantly potentiate norepinephrine release ...

The nucleus accumbens shell is a site of converging inputs during memory processing for emotional events. The accumbens receives input from the nucleus of the solitary tract (NTS) regarding changes in peripheral autonomic functioning following emotional arousal. The shell also receives input from the amygdala and hippocampus regarding affective and contextual attributes of new learning experiences. The successful encoding of affect or context is facilitated by activating noradrenergic systems in either the amygdala or hippocampus. Recent findings indicate that memory enhancement produced by activating NTS neurons, is attenuated by suppressing accumbens functioning after learning. This finding illustrates the significance of the shell in integrating information from the periphery to modulate memory for arousing events. However, it is not known if the accumbens shell plays an equally important role in consolidating information that is initially processed in the amygdala and hippocampus. The present study determined if the convergence of inputs from these limbic regions within the nucleus accumbens contributes to successful encoding of emotional events into memory. Male Sprague-Dawley rats received bilateral cannula implants 2 mm above the accumbens shell and a second bilateral implant 2 mm above either the amygdala or hippocampus. The subjects were trained for 6 days to drink from a water spout. On day 7, a 0.35 mA footshock was initiated as the rat approached the spout and was terminated once the rat escaped into a white compartment. Subjects were then given intra-amygdala or hippocampal infusions of PBS or a dose of norepinephrine (0.2 μg) previously shown to enhance memory. Later, all subjects were given intra-accumbens infusion of muscimol to functionally inactivate the shell. Muscimol inactivation of the accumbens shell was delayed to allow sufficient time for norepinephrine to activate intracellular cascades that lead to long-term synaptic modifications involved in forming new memories. Results show that memory improvement produced by infusing norepinephrine in either the amygdala or hippocampus is attenuated by interrupting neuronal activity in the shell 1 or 7 7 h following amygdala or hippocampus activation. These findings suggest that the accumbens shell plays an integral role modulating information initially processed by the amygdala and hippocampus following exposure to emotionally arousing events. Additionally, results demonstrate that the accumbens is involved in the long-term consolidation processes lasting over 7 h.