Search

Supplemental Digital Content is available in the text.Contextual information is represented in the hippocampus (HPC) partially through the recruitment of distinct neuronal ensembles. It is believed that reactivation of these ensembles underlies memory retrieval processes. Recently, we showed that norepinephrine input from phasic locus coeruleus activation induces hippocampal plasticity resulting in the recruitment of new neurons and disengagement from previously established representations. We hypothesize that norepinephrine may provide a neuromodulatory mnemonic switch signaling the HPC to move from a state of retrieval to encoding in the presence of novelty, and therefore, plays a role in memory updating. Here, we tested whether bilateral dorsal dentate gyrus (dDG) infusions of the β-adrenergic receptor (BAR) agonist isoproterenol (ISO), administered prior to encoding or retrieval, would impair spatial working and reference memory by reverting, the system to encoding (thereby recruiting new neurons) potentially interfering with the retrieval of the previously established spatial ensemble. We also investigated whether dDG infusions of ISO could promote cognitive flexibility by switching the system to encoding when it is adaptive (ie, when new information is presented, eg, reversal learning). We found that intra-dDG infusions of ISO given prior to retrieval caused deficits in working and reference memory which was blocked by pretreatment with the BAR-antagonist, propranolol (PRO). In contrast, ISO administered prior to reversal learning led to improved performance. These data support our hypothesis that norepinephrine serves as a novelty signal to update HPC contextual representations via BAR activation-facilitated recruitment of new neurons. This can be both maladaptive and adaptive depending on the situation.

Type 2 diabetes mellitus has steadily increased in prevalence over the past five decades. Among the health risks associated with this disorder are cognitive decline and are increased risk of developing dementia. To further investigate the link between diabetes and cognition, here we test memory performance and hippocampal function in the Goto-Kakizaki (GK) rat, a robust model of diabetes. Relative to age-matched Wistar rats, GK rats show impairments in a conjunctive memory task that requires discriminating objects not only on the basis of their physical characteristics, but also on the basis of where and when they were last seen. Concomitant to these deficits are changes in the pattern of expression of Egr1(an immediate-early gene critical for memory) in dentate gyrus granule cells, consistent with dentate hypoactivity leading to unstable hippocampal representations. These data support the hypothesis that diabetes confers a phenotype of accelerated senescence on the hippocampus, and help to link this disorder with changes in hippocampal circuits.

Here, we present a protocol for inducing selective lesions in the hippocampal formation of Japanese quail (Coturnix japonica), coupled with associated behavioral testing. We first describe the surgical procedure for aspiration lesions in Japanese quail. We then detail two well-known hippocampus-dependent behavioral tests adapted to birds—foraging array (FA) and spontaneous object recognition (SOR). This protocol is adapted from those used in mammals and can be used to study the involvement of Japanese quail memory centers in declarative memory.

Long‐term potentiation (LTP) in the hippocampus has been associated with changes in synaptic morphology. Whether these changes are LTP‐dependent or simply a result of electrophysiological stimulation has not yet been fully determined. This study involved an examination of synaptic morphology in the rat dentate gyrus 24 h after electrophysiological stimulation sufficient to induce LTP. In one group, ketamine, a competitive NMDA antagonist, was injected prior to stimulation to block the formation of LTP. Synaptic morphological quantification included estimating the total number of synapses per neuron, determining synaptic curvature and the presence of synaptic perforations, and measuring the maximal PSD profile length of the synapses. The results indicated that most of the changes observed following the induction of LTP (increases in the proportion of concave‐shaped synapses, increases in perforated concave synapses, and a decrease in the length of nonperforated concave synapses) are not observed under ketamine blockade, suggesting that they are LTP‐specific and not simply the result of tetanic stimulation. Ketamine was associated, however, with several novel structural changes including a decrease in the length of the perforations in the concave perforated synapses, a reduction in the number of convex perforated synapses, and a nonlayer‐specific increase in synaptic length compared to controls. Based on previous research, this combination of morphological characteristics is potentially less efficacious, which suggests that synapses that are tetanized but not potentiated, due to pharmacological blockade, appear to undergo opposing, compensatory, or homeostatic changes. These results support the suggestion that synaptic morphology changes are both stimulation‐ and area‐specific, are highly complex, and depend on the specific local physiology. Synapse 47:77–86, 2003. © 2002 Wiley‐Liss, Inc.

Estimating synaptic density is central to any examination of synaptic change. Barring techniques involving exhaustive sectioning, the traditional method for this estimation is the double dissector technique, which derives a ratio of synapses per neuron. This ratio, however, may not always equate to an absolute number of synapses. In contrast, the unbiased brick, while free of these problems, is limited by changes in reference space and cannot provide information on synaptic connectivity. Thus, the ideal analysis is to derive both synaptic measures. When these measures agree, one can discount changes in extraneous factors influencing synaptic counts.