Effects of hippocampal lesions on patterned motor learning in the rat.

Motor skill learning in rats has been linked to cerebellar function as well as to cortical and striatal influences. The present study evaluated the contribution of the hippocampus to motor learning. Adult male rats received electrolytic lesions designed to selectively destroy the hippocampus; a sham-lesioned group of animals served as a control. The animals with hippocampal lesions acquired a patterned motor learning task as well as sham controls. In contrast, rats with hippocampal lesions were impaired in spatial, but not cued, learning in the Morris water maze. In addition, lesioned rats showed profound impairment in the novel object recognition memory task, when a 1-h delay was used between training and testing. Taken together, these results suggest that the hippocampus is not necessary during acquisition of the motor learning task.

Acute peroxide treatment of rat hippocampal slices induces adenosine-mediated inhibition of excitatory transmission in area CA1.

Brief exposure to conditions that generate free radicals inhibits synaptic transmission in hippocampal slices, most likely via a presynaptic mechanism. Because other physiologically stressful conditions that generate free radicals, such as hypoxia or ischemia, stimulate the release of adenosine from brain slices, we determined whether increases in extracellular adenosine mediate the presynaptic inhibition of excitatory transmission induced by peroxide treatment. Simultaneous addition of hydrogen peroxide (0.01%) and ferrous sulfate (100 microM) resulted in a >80% decrease in synaptic potentials recorded in the CA1 region of hippocampal slices of adult male rats. Treatment with theophylline (200 microM), a non-selective adenosine receptor antagonist, or 8-cyclopentyl-1,3-dipropylxanthine (100 nM), a selective adenosine A1 receptor antagonist, prior to and during hydrogen peroxide superfusion prevented the inhibition. These results demonstrate that acute exposure to hydrogen peroxide induces an adenosine-mediated decrease in synaptic transmission in hippocampal slices.

Exposing rats to a predator blocks primed burst potentiation in the hippocampus in vitro.

This study evaluated the effects of acute psychological stress (cat exposure) in adult male rats on electrophysiological plasticity subsequently assessed in the hippocampus in vitro. Two physiological models of memory were studied in CA1 in each recording session: (1) primed burst potentiation (PBP), a low-threshold form of plasticity produced by a total of five physiologically patterned pulses; and (2) long-term potentiation (LTP), a suprathreshold form of plasticity produced by a train of 100 pulses. Three groups of rats were studied: (1) undisturbed rats in their home cage (home cage); (2) rats placed in a chamber for 75 min (chamber); and (3) rats placed in a chamber for 75 min in close proximity to a cat (chamber/stress). At the end of the chamber exposure period, blood samples were obtained, and the hippocampus was prepared for in vitro recordings. Only the chamber/stress group had elevated (stress) levels of corticosterone. The major finding was that PBP, but not LTP, was blocked in the chamber/stress group. Thus, the psychological stress experienced by the rats in response to cat exposure resulted in an inhibition of plasticity, which was localized to the intrinsic circuitry of the hippocampus. This work provides novel observations on the effects of an ethologically relevant stressor on PBP in vitro and of the relative insensitivity of LTP to being modulated by psychological stress. We discuss the relevance of these electrophysiological findings to our behavioral work showing that predator stress impairs spatial memory.

Norepinephrine release in the amygdala in response to footshock stimulation.

Extensive evidence suggests that many drugs and hormones influence memory storage by modulating training-induced release of norepinephrine (NE) within the amygdala. This experiment used in vivo microdialysis and high-performance liquid chromatography to examine norepinephrine NE release in the amygdala induced by footshock stimulation typically used in inhibitory avoidance training. Sprague-Dawley rats were implanted bilaterally with cannulae aimed at the amygdala. One to two weeks later, microdialysis probes were inserted (unilaterally) and the animals were placed in a box with a stainless-steel grid floor through which a single footshock (0.55 mA, 1.0 s) was administered either 45.5 (N = 5) or 180.5 (N = 4) min later. Samples were collected and analyzed at 15-min intervals. In both groups, the footshock stimulation increased NE levels to approximately 75% above basal levels in the first sample collected after the footshock and the levels returned to baseline within 30 min. The findings are consistent with pharmacological evidence suggesting that NE released by arousing stimulation is involved in regulating memory storage.

The effects of intra-amygdala infusion of the AMPA receptor antagonist CNQX on retention performance following aversive training.

The aim of these experiments was to determine whether impaired retention performance in aversively motivated tasks, induced by blockade of amygdala AMPA receptors, is due to influences on mechanisms underlying memory retrieval or to other influences on performance. Rats received either footshock escape training (1 or 10 trials), or no foot shock, in a two-compartment straight alley and bilateral intra-amygdala infusions of the AMPA receptor antagonist CNQX (0.5 microgram) were subsequently administered prior to inhibitory avoidance retention testing 8 days later. The CNQX impaired, but did not block, inhibitory avoidance retention performance as indicated by the initial latencies to enter the shock compartment. The animals were then retained in the alley until they remained in the starting compartment for 100 consecutive s and entries into the shock compartment were recorded as errors. In both the controls and CNQX-treated groups, increases in amount of original training resulted in fewer errors, indicating memory for the escape training. Furthermore, regardless of the amount of original training (i.e., 0, 1, or 10 trials), CNQX-treated groups made more errors. Other experiments examined intra-amygdala CNQX effects on reactivity to footshock, locomotor activity, and anxiety. CNQX decreased reactivity to footshock, blocked shock-induced decreases in locomotor activity, and had an anxiolytic effect in an elevated plus maze comparable to that induced by midazolam (0.5 microgram). These findings suggest that intra-amygdala infusions of CNQX prior to retention testing affect inhibitory avoidance retention performance following aversive training by altering locomotor activity, reducing sensitivity to footshock, and reducing anxiety. The implications of these findings for hypotheses concerning amygdala function in aversively motivated learning and memory is discussed.

Bicuculline administered into the amygdala blocks benzodiazepine-induced amnesia.

This experiment investigated the effect of intra-amygdala administration of the GABAergic antagonist bicuculline methiodide on benzodiazepine-induced amnesia. Male Sprague-Dawley rats were implanted bilaterally with cannulae aimed at the amygdala and allowed to recover for 1 week. Ten minutes before training in a continuous multiple trial inhibitory avoidance task a buffer solution or bicuculline methiodide (56 pmol/0.5 microliters) was injected bilaterally into the amygdala and this injection was immediately followed by a systemic injection of saline or midazolam (1.0 mg/kg). In comparison with saline controls, midazolam-treated animals required more trials to reach the acquisition criterion of remaining in the starting chamber for 100 s. The midazolam effect on acquisition was not attenuated by intra-amygdala infusion of bicuculline methiodide, suggesting that the midazolam-induced changes in acquisition behavior do not involve the amygdaloid GABAergic system. On a 48-h retention test the performance of the midazolam-treated animals was significantly poorer than that of the controls. However, the retention performance of animals given intra-amygdala injections of bicuculline methiodide prior to the systemic injection of midazolam was comparable to that of the saline controls. These results suggest that the amygdaloid GABAergic system mediates the impairing effects of midazolam on retention of inhibitory avoidance training.