These results with systemic and intracerebral drug infusion suggest that 5-HT(1A) receptors localised in the amygdala are not involved in the pain inhibitory processes that are "recruited" during aversive situations. However, activation of these receptors does phasically increase anxiety. Although the intrinsic antinociceptive properties of systemically administered midazolam confounded interpretation of its effects on OAIA, intra-amygdala injections of this compound suggest that benzodiazepine receptors in this brain region modulate both the antinociceptive and behavioural (anxiety) responses to the EPM.

Emotional enhancement of memory by noradrenergic mechanisms is well-described, but the long-term consequences of such enhancement are poorly understood. Over time, memory traces are thought to undergo a neural reorganization, that is, a systems consolidation, during which they are, at least partly, transferred from the hippocampus to neocortical networks. This transfer is accompanied by a decrease in episodic detailedness. Here we investigated whether norepinephrine (NE) administration into the basolateral amygdala after training on an inhibitory avoidance discrimination task, comprising two distinct training contexts, alters systems consolidation dynamics to maintain episodic-like accuracy and hippocampus dependency of remote memory. At a 2-d retention test, both saline-and NE-treated rats accurately discriminated the training context in which they had received footshock. Hippocampal inactivation with muscimol before retention testing disrupted discrimination of the shock context in both treatment groups. At 28 d, saline-treated rats showed hippocampus-independent retrieval and lack of discrimination. In contrast, NE-treated rats continued to display accurate memory of the shock-context association. Hippocampal inactivation at this remote retention test blocked episodic-like accuracy and induced a general memory impairment. These findings suggest that the NE treatment altered systems consolidation dynamics by maintaining hippocampal involvement in the memory. This shift in systems consolidation was paralleled by time-regulated DNA methylation and transcriptional changes of memory-related genes, namely Reln and Pkmζ, in the hippocampus and neocortex. The findings provide evidence suggesting that consolidation of emotional memories by noradrenergic mechanisms alters systems consolidation dynamics and, as a consequence, influences the maintenance of long-term episodic-like accuracy of memory.basolateral amygdala | norepinephrine | memory accuracy | hippocampus | systems consolidation E motionally arousing experiences are well-retained in memory (1, 2). Beyond their increased strength, emotionally enhanced memories are also often characterized by increased vividness and the subjective feeling of remembering (3, 4). Both animal and human research indicate that noradrenergic activation of the basolateral amygdala (BLA) enhances memory of emotionally arousing experiences by regulating neural plasticity and information storage processes in other brain regions (5-12). A majority of studies investigating the effects of noradrenergic activation of the BLA in memory have focused on episodic (declarative) or contextual tasks that involve functioning of the hippocampus (13-17). The BLA sends extensive projections to the hippocampus (18) and has a major impact on hippocampal functioning (19-21).There is extensive evidence that the memory enhancement induced by BLA activation by norepinephrine (NE) administration or emotional arousal during or shortly after learning involves hippocampal activation (20,(22)(23)(24). This activa...

Stereotaxic surgery for the implantation of cannulae into specific brain regions has for many decades been a very successful experimental technique to investigate the effects of locally manipulated neurotransmitter and signaling pathways in awake, behaving animals. Moreover, the stereotaxic implantation of electrodes for electrophysiological stimulation and recording studies has been instrumental to our current understanding of neuroplasticity and brain networks in behaving animals. Ever-increasing knowledge about optimizing surgical techniques in rodents 1-4 , public awareness concerning animal welfare issues and stringent legislation (e.g., the 2010 European Union Directive on the use of laboratory animals 5 ) prompted us to refine these surgical procedures, particularly with respect to implementing new procedures for oxygen supplementation and the continuous monitoring of blood oxygenation and heart rate levels during the surgery as well as introducing a standardized protocol for post-surgical care. Our observations indicate that these modifications resulted in an increased survival rate and an improvement in the general condition of the animals after surgery (e.g. less weight loss and a more active animal). This video presentation will show the general procedures involved in this type of stereotaxic surgery with special attention to our several modifications. We will illustrate these surgical procedures in rats, but it is also possible to perform this type of surgery in mice or other small laboratory animals by using special adaptors for the stereotaxic apparatus 6 . Video LinkThe video component of this article can be found at http://www.jove.com/video/3528/ Protocol Note: Antiseptic techniques should be employed during the whole procedure. All the instruments and materials (cotton-tipped swabs, gauze, etc.) that will be used during the surgery should be sterilized by autoclaving. A surgical mask, hair bonnet and sterile gloves should be worn. The working area and the stereotaxic apparatus should be cleaned thoroughly, and disinfected with a 70% ethanol solution. 2. Place the cannula in its support and check if it is straight. 3. Turn on the gas system -mixture of ambient air and oxygen (30-35% of total flow should be oxygen). 4. Weigh the rat and administer the anesthetic. We are using a mixture of ketamine (37.5 mg/kg) and dexmedetomidine (0.25 mg/kg) injected subcutaneously. For different anesthesia protocols, see Flecknell 4 and Hellebrekers et al. 7 . 5. After the rat lost consciousness, shave the head area going from the ears to just in between the eyes with an electric razor. 6. Place the rat on the heating pad, with its nose in front of the air tubing. Use an oximeter to ensure that the rat has an adequate blood oxygenation level (should not drop <90%). Please follow the manufacturer's instructions for proper use of equipment. 7. Apply eye cream (Duratears Z, Alcon) on both corneas to avoid dehydration. 8. Check the rat's reflexes (tail reflex or toe-pinch reflex, as demonstrated in Walantu...