Faculty Bibliography

Although long-term potentiation (LTP) has been demonstrated in a number of subcortical sites in chronic preparations, there have been no demonstrations of LTP in the neocortex of chronic preparations. Even neocortical slice and acute preparations often require a drug-induced suppression of inhibition before LTP effects can be reliably induced. We have attempted to induce LTP in neocortical sites in 7 different experiments using chronically prepared adult rats. We were unable to obtain any evidence, even a trend, for the induction of LTP. The following manipulations were tested: (1) standard stimulation train parameters that have been shown to be highly effective in subcortical and hippocampal sites; (2) a 10-fold increase in the intra-train pulse durations; (3) variations in train pulse frequency (1 Hz to 300 Hz) and train duration (100 ms to 15 min); (4) co-activation of multiple inputs by stimulation of combinations of cortical sites or cortical and thalamic sites; (5) reduction of inhibition by administration of picrotoxin; 5) Housing of animals in an enriched environment; (6) utilization of the neocortical stimulation trains as a cue in a learning task; (7) application of pilocarpine to co-activate cholinergic systems. Although none of these manipulations produced LTP, the application of pilocarpine did facilitate the induction of a long-lasting depression effect. These findings contrast with the results obtained from anesthetized rats and from studies using brain slices, where LTP can be reliably induced. These results are discussed in light of other recent findings with respect to LTP and LTD effects

Long-term potentiation is widely studied as a memory model, and has been demonstrated in a number of subcortical sites in both acute and chronic preparations. In the neocortex, however, most of the demonstrations of LTP have been in neocortical slice or acute preparations, and even these have often required a drug-induced attenuation of inhibition before the LTP could be reliably expressed. In this paper we show that LTP can be reliably expressed in adult rats in a number of neocortical sites, both ipsilateral and contralateral to the site of callosal stimulation. We also show that, when recording field potentials, LTP is expressed roughly equally at all cortical depths. In a third experiment, we monitored input/output (I/O), paired-pulse inhibition and short-term potentiation effects over the course of LTP induction. The ipsilateral responses were, as expected, of shorter latency and larger amplitude than contralateral responses. They also showed small spike-like components that correlated with cell discharge. Nevertheless, the contralateral responses tended to show the largest LTP effects. The paired pulse effect was mainly depression, lasting for up to 3000 ms, at both ipsilateral and control sites. The short-term potentiation components were best fit by two summed exponentials with time constants of about 70 s and 12 min. The LTP effect lasted at least two h which was the longest period monitored in these experiments

Although olfactory associative conditioning in newborn rats produces marked structural and functional changes in the olfactory bulb, recent evidence suggests that extrabulbar circuits must be involved in storing these early memories. The present experiments examined the role of the amygdala complex on early olfactory learning. Bilateral amygdala lesions or sham lesions were performed on Postnatal Day (PN) 5. On PN6, pups were trained in a standard classical conditioning paradigm associating odor with tactile stimulation. Behavioral testing on PN7 revealed that amygdala lesions blocked odor preferences but had no effect on conditioned behavioral activation. Similar sized neocortical lesions did not impair odor preferences. Importantly, amygdala lesion effects on learned odor preferences could be reversed by extensive overtraining. These results suggest that the amygdala complex plays a critical role in modulating associative learning as early as the first postnatal week in the rat

Adult male Wistar rats were trained in a simple odor detection task, with peppermint odor serving as either an S+, S- or as a randomly presented odor. Twenty-four hours after the last training session, rats were injected with [14C]2-deoxyglucose and exposed to the odor. Mean relative 2-deoxyglucose uptake to the odor was enhanced in the pars dorsalis of the anterior olfactory nucleus of S+ and S- trained rats compared to controls. In contrast, no differences in uptake were detected in either odor-specific focal regions of the olfactory bulb glomerular layer, the pyriform cortex, or the hippocampus

Association of odor and reward during the early postnatal period modifies rat pup behavioral responses and olfactory bulb neural responses to subsequent presentations of that odor. Recent evidence has shown that olfactory bulb output neurons, mitral/tufted cells, receive convergent odor and reward inputs. The present report demonstrates that contiguous odor-reward pairings prevent mitral/tufted cell habituation to the odor that normally occurs to repeated odor-only stimulation. It is hypothesized that the maintenance of olfactory bulb responses to conditioned odors during training may allow for activation of long-term memory mechanisms

Wistar rat pups were implanted with bilateral olfactory bulb cannulas on postnatal day 5 (PN5). On PN6, pups were trained in an olfactory classical conditioning task with peppermint odor as the CS and tactile stimulation/stroking as the UCS. Pups were randomly assigned to either PAIRED, BACKWARD or ODOR-only conditions. Half the pups in each group received intrabulbar infusions of 100 microM propranolol and half received intrabulbar infusions of saline during the training session. Propranolol infusions blocked acquisition of the learned odor preference expressed by PAIRED saline-infused pups. Diffusion of the infusate was checked in additional pups by infusing [3H]NE and performing LSC analysis. Infusate concentration did not significantly differ between the anterior and posterior halves of the bulb, but were sharply lower in the olfactory peduncle and more posterior areas. The results suggest that olfactory bulb NE is critical for early olfactory learning

In neonatal rats, norepinephrine (NE) is necessary and sufficient for the acquisition of an olfactory preference and its associated olfactory bulb neural modifications as assessed by [(14)C] 2-deoxyglucose (2-DG) and electrophysiology. In the present studies, we assessed the influence of NE on the expression of a conditioned odor preference and its associated olfactory bulb neural modifications in neonatal rats. On Postnatal Day 5 (PN 5), pups were trained to prefer an odor in a 1-h classical conditioning paradigm. Experimental paired odor-stroke pups received 20 forward pairings of a 10-sec peppermint odor and a 9-sec reinforcing tactile stimulation (stroking). Control pups received either random stroke-odor pairings or were naive (received neither the odor nor stroking). The next day (PN 6), the pups were injected with either an NE beta-receptor antagonist, (propranolol or timolol) or saline, 1 h prior to testing. The pups were tested for a behavioral olfactory preference and assessed for differential olfactory bulb activity with [(14)C] 2-DG autoradiography. The results indicate that NE is not necessary for the expression of the learned neurobehavioral response

Newborn rat pups can learn to either approach or avoid odor cues through associative conditioning. The present results demonstrate that preference conditioning and avoidance conditioning both modify olfactory bulb responses (focal 2-deoxyglucose uptake and mitral-tufted cell single unit responses) to the conditioned odor. Despite opposing behavioral responses to the conditioned odor, however, olfactory bulb neural responses did not detectably differ between learned odor cues signaling approach and those signaling avoidance. Control pups exhibited neither the behavioral nor neural changes. Furthermore, both the behavioral and neural changes to these odor cues could be extinguished. These results suggest that the olfactory bulb in neonates may code learned odor importance, but specific information attached to that importance may require processing in other brain regions

One of the circuits modified by early olfactory learning is in the olfactory bulb. Specifically, response patterns of mitral-tufted cells are modified by associative conditioning during the early postnatal period. In addition, previous work has demonstrated that mitral-tufted cell single units respond to both olfactory conditioned stimuli and rewarding stimulation of the medial forebrain bundle-lateral hypothalamus (MFB-LH). The present study suggests that norepinephrine beta-receptor activation is required for early olfactory learning using MFB-LH stimulation as reward. Propranolol injected before odor-MFB-LH pairings blocks the acquisition of conditioned behavioral responses and their neural correlates to the conditioned odor. Furthermore, propranolol blocks a specific class of the mitral-tufted cell responses to MFB-LH reward stimulation. The relationship of this response to reward and early learning is discussed