Faculty Bibliography

Unilateral olfactory deprivation for the first 3 postnatal weeks results in an enhancement of granule cell mediated, feedback inhibition of mitral cells in the rat olfactory bulb. Granule cells are excited by mitral cells by both non-NMDA and NMDA receptors. The present report describes the effect of the NMDA antagonist MK-801 (0.75 mg/kg) on the expression of deprivation enhanced inhibition. The results demonstrate that (1) enhancement of lateral olfactory tract paired-pulse inhibition of evoked potentials in deprived bulbs was stimulus intensity dependent, with the greatest difference expressed at highest stimulus intensities; (2) MK-801 reduced inhibition in both undeprived and deprived bulbs in a stimulus intensity dependent manner, with the greatest reduction occurring at highest stimulus intensities; (3) MK-801 eliminated the stimulus intensity effect on inhibition in both groups; and (4) following MK-801, deprived bulbs showed the same or less inhibition than undeprived bulbs

Wistar rat pups, aged Postnatal Day 5, were trained in an olfactory associative learning task with citral odor as the conditioned stimulus (CS) and intraoral infusions of milk as the unconditioned stimulus (US). Following a 30-min training session, pups were injected with either the norepinephrine beta-receptor antagonist propranolol or the beta-receptor agonist isoproterenol. Pups were tested 24 hr later for an acquired relative odor preference for the CS. Propranolol injected immediately following training impaired memory for the CS in a dose-dependent manner. This posttraining effect lasted less than 4 hr. Isoproterenol injected immediately after training also impaired memory performance, even at very low doses. These results suggest that posttraining levels of norepinephrine play a critical role in memory consolidation in the newborn, with elevations or decrements in noradrenergic activity resulting in impaired memory

On postnatal day 4 (PN4) Wistar rat pups were anesthetized and received bilateral infusions of 6-OHDA into the locus coeruleus or received vehicle infusions. On PN6 pups were trained in a classical conditioning paradigm with intra-oral milk infusions as the UCS and citral odor as the CS. Pups were trained in either 'paired', 'odor-only', 'milk-only' or 'backward' (milk then odor) conditions. On PN7 acquisition of a learned odor preference to the CS was tested in a two-odor choice test. HPLC analysis showed that locus coeruleus lesions significantly reduced olfactory bulb NE content but had no effect on olfactory bulb DA or 5-HT levels compared to controls. Pups receiving locus coeruleus lesions did not differ in behavioral response patterns during training compared to their littermate, vehicle controls. However, locus coeruleus lesions impaired acquisition of conditioned odor preferences. These results suggest that NE output from the locus coeruleus is critical for early olfactory learning

Describes 2 simulations of neural transmission for use in an introductory psychology class. The simulations illustrate the complex coding properties of a single neuron, including how excitatory and inhibitory postsynaptic potentials accumulate to produce an action potential. A follow-up exercise, using the framework of the children's game 'Musical Chairs,' illustrates synaptic transmission, including the effects of psychoactive drugs at the synapse. The effectiveness of the exercise was assessed in 8 sections of introductory psychology courses. Responses to a multiple-choice quiz administered 1 wk after the exercise suggest that the exercise improved students' understanding of the complexity of coding.

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

Mammalian neonates have been simultaneously described as having particularly poor memory, as evidenced by infantile amnesia, and as being particularly excellent learners with unusually plastic nervous systems that are easily influenced by experience. An understanding of the neurobiological constraints and mechanisms of early learning may contribute to a unified explanation of these two disparate views. Toward that end, we review here our work on the neurobiology of learning and memory in neonates. Specifically, we have examined the neurobiology of early learning using an olfactory classical conditioning paradigm. Olfactory classical conditioning in neonates at the behavioral level conforms well with the requirements and outcomes of classical conditioning described in adults. Furthermore, specific neural correlates of this behavioral conditioning have been described including anatomical and physiological changes, neural pathways, and modulatory systems. In this Review, we outline the behavioral paradigm, the identified neural correlates, and apparent mechanisms of this learning. Finally, we compare the neurobiology of early learning with that reported for mature animals, with specific reference to the role of US-CS convergence, memory modulation, consolidation, and distributed memory

Use of learned odor cues by newborn rats is critical for pup survival. Rat pups acquire approach responses to maternal odors through an associative conditioning mechanism. This learned behavioral response is accompanied by a modification of olfactory bulb neural response patterns to the learned odor. Both the behavioral and neural response changes involved and require norepinephrine release in the olfactory bulb. The source of this norepinephrine is the locus coeruleus. It is proposed that the unique response properties of the locus coeruleus during the early postnatal period in the rat may facilitate acquisition of these critical early memories

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

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