OTTO LABORATORY

Tim Otto, Ph.D.

Program in Behavioral Neuroscience

Department of Psychology

Rutgers University

New Brunswick, NJ 08903

Send us email by clicking here

Current Research | Publications | Personnel | Vita | Undergrad / Grad Course Info

Current Research:

Broadly defined, the primary focus of our work is to explore the ways in which information is acquired and stored in the mammalian brain. Most of these studies involve an examination of the neural substrates of olfactory (odor) memory in the rat. Briefly, we focus mainly on olfactory memory for two reasons. First, rats exhibit a remarkable facility in learning when trained in tasks which use odors as stimuli. Second, the brain areas participating in the detection and analysis of odors are intimately and reciprocally connected with several brain areas known to play a prominent role in learning, including the amygdala, the hippocampus, and the rhinal cortical areas (perirhinal and entorhinal cortex).

These studies span several levels of neurobiological analysis. We are currently examining the participation of various brain regions in olfactory memory through neuropsychological (lesion) studies, electrophysiological studies examining the response properties of neurons in the amygdala, hippocampus, and rhinal cortical areas in awake, behaving rats during learning, and immunohistochemical studies examining the extent to which learning results in an activation of specific genes within brain cells. We are also beginning a series of studies examining the extent to which, following experimentally-induced damage, regeneration of olfactory receptor neurons and the subsequent reinnervation of the olfactory bulb is related to a recovery of function, and whether this regeneration and recovery of function can be pharmacologically enhanced. Many of these findings are explained in more detail under the Publications link.

These studies have been supported by grants IBN0316247, IBN9514526 and IBN9817145 from the National Science Foundation, a Discovery Award from Johnson & Johnson Inc., and the Busch Grant Program at Rutgers University.

Return to Top

Publications: Feel free to Email me if you would like a reprint of any of the following publications.

Journal Articles: The abstracts for many of these publications are available by clicking on the "Abstract" link at the end of the reference.

Yoon, T., & Otto, T. (2007). Differential contributions of dorsal vs. ventral hippocampus to auditory trace fear conditioning. Neurobiology of Learning and Memory, 87, 464-475. Full Text (pdf format)

Otto, T., & Poon, P. (2006). Dorsal hippocampal contributions to unimodal contextual conditioning. Journal of Neuroscience, 26, 6603-6609. Full Text (pdf format)

Yoon, T., & Otto, T. (Under Review). Neural substrates of olfactory discrimination learning with auditory secondary reinforcement. II. Contributions of the perirhinal cortex.

Nicot, A., Otto, T., Brabet, P., & DiCicco-Bloom, E.M. (2004). Altered social behavior in pituitary adenylate cyclase-activating polypeptide Type-I receptor-deficient mice. Journal of Neuroscience, 24, 8786-8795.

Cousens, G., & Otto, T. (2003). Contributions of orbitofrontal cortex and basolateral amygdaloid complex to olfactory discrimination learning with auditory secondary reinforcement. Integrative Physiological & Behavioral Science, 38, 272-294.

Herzog, C.D., & Otto, T. (2002). Administration of transforming growth factor alpha enhances anatomical and behavioral recovery following olfactory nerve transection. Neuroscience, 113, 569-580. Abstract

Schettino, L.F. , & Otto, T. (2001). Patterns of Fos expression in the amygdala and ventral perirhinal cortex induced by training in an olfactory fear conditioning paradigm. Behavioral Neuroscience, 115(6), 1257-1272. Abstract

Otto, T., & Giardino, N. (2001). Pavlovian conditioning of emotional responses to olfactory and contextual stimuli: A potential model for the development and expression of chemical intolerance.  Annals of the New York Academy of Sciences, 933, 291-309. Abstract

Otto, T., Cousens, G., & Herzog, C.D. (2000). Behavioral and neuropsychological foundations of olfactory  fear conditioning. Behavioural Brain Research, 110, 119-128. Abstract

Herzog, C.D., & Otto, T. (1999). Regeneration of olfactory receptor neurons following chemical lesion: Time course and enhancement with growth factor administration. Brain Research, 849, 155-161. Full Text (pdf format)

Cousens, G., & Otto, T. (1998). Both pre- and post-training lesions of the basolateral amygdala abolish the expression of olfactory and contextual fear conditioning. Behavioral Neuroscience, 112, 1092-1103. Abstract

Herzog, C.D., & Otto, T. (1998). Contributions of anterior perirhinal cortex to olfactory and contextual fear conditioning. Neuroreport, 9, 1855-1859. Abstract

Flaherty, C.F., Coppotelli, C., Hsu, D., & Otto, T. (1998). Excitotoxic lesions of the hippocampus disrupt instrumental but not consummatory contrast. Behavioural Brain Research, 93, 1-9.

Cousens, G., & Otto, T. (1998). Long-term potentiation and its transient suppression in the rhinal cortices induced by theta-related stimulation of hippocampal field CA1. Brain Research, 780, 95-101.  Full Text (pdf format)

Otto, T., & Garruto, D. (1997). Rhinal cortical lesions impair simultaneous olfactory discrimination learning in rats. Behavioral Neuroscience, 111, 1-5. Abstract

Otto, T., Cousens, G., & Rajewski, K. (1997). Odor-guided fear conditioning. I. Acquisition, retention, and latent inhibition. Behavioral Neuroscience, 111, 1257-1264. Abstract

Herzog, C.D., & Otto, T. (1997). Odor-guided fear conditioning. II. Lesions of anterior perirhinal cortex disrupt fear conditioned to the explicit CS but not to the training context. Behavioral Neuroscience, 111, 1265-1274. Abstract

Otto, T., Wolf, D., & Walsh, T. (1997). Combined lesions of perirhinal and entorhinal cortex impair rats' performance in two versions of the spatially-guided radial arm maze. Neurobiology of Learning and Memory, 68, 21-31. Abstract

Young, B.J., Otto, T., Fox, G., & Eichenbaum, H. (1997). Memory representation in the parahippocampal region. Journal of Neuroscience, 17, 5183-5195. Abstract

Eichenbaum, H., Otto, T., & Cohen, N.J. (1996). The hippocampal system: Dissociating its functional components and recombining them in the service of declarative memory. Behavioral and Brain Sciences, 19, 762-776.

Zyzak, D.R., Otto, T., Eichenbaum, H., & Gallagher, M. (1995). Cognitive decline associated with normal aging in rats: A neuropsychological approach. Learning & Memory, 2, 1-16. Abstract

Nagahara, A. H., Otto, T., & Gallagher, M. (1995). Entorhinal lesions impair performance in two versions of place learning in the Morris water maze. Behavioral Neuroscience 109, 3-9. Abstract

Eichenbaum, H., Otto, T., & Cohen, N.J. (1994). Two functional components of the hippocampal memory system. Behavioral and Brain Sciences, 17(3),449-517. Abstract

Otto, T., & Eichenbaum, H. (1992). Neuronal activity in the hippocampus during delayed non-match to sample performance in rats: Evidence for hippocampal processing in recognition memory. Hippocampus, 2(3), 324-334. Abstract

Otto, T., & Eichenbaum, H. (1992). Complementary roles of orbital prefrontal cortex and the perirhinal/entorhinal cortices in an odor-guided delayed non-matching to sample task. Behavioral Neuroscience, 106, 763-775. Abstract

Eichenbaum, H., Otto, T. & Cohen, N.J. (1992). The Hippocampus - What Does It Do? Behavioral and Neural Biology, 57, 1-35.

Otto, T., Schottler, F., Staubli, U., Eichenbaum, H., & Lynch, G. (1991). The hippocampus and olfactory discrimination learning: Effects of entorhinal cortex lesions on odor memory in a successive-cue, go, no-go task. Behavioral Neuroscience, 105, 111-119. Abstract

Otto, T., Eichenbaum, H. Wiener, S.I., & Wible, C.G. (1991). Learning-related patterns of CA1 spike trains parallel stimulation parameters optimal for inducing hippocampal long-term potentiation. Hippocampus 1, 181-192. Abstract

McCollum, J., Larson, J., Otto, T., Schottler, F., Granger, R., & Lynch, G. (1991). Short-latency single unit processing in olfactory cortex. Journal of Cognitive Neuroscience, 3, 293-299. Abstract

Granger, R., Staubli, U., Powers, H., Otto, T., Ambros-Ingerson, J., & Lynch, G. (1991). Behavioral tests of a prediction from a cortical network simulation. Psychological Science, 2, 116-118. Abstract

Mair, R.G., Otto, T.A., Knoth, R., Rabchenuk, S., & Langlais, P. (1991). An analysis of aversively conditioned learning and memory in rats recovered from pyrithiamine-induced thiamine deficiency. Behavioral Neuroscience, 105, 351-359. Abstract

Fuld, K., Otto, T.A., & Slade, C.W. (1986). The spectral responsivity of the white-black channel. Journal of the Optical Society of America, A, 3, 1182-1188.

Fuld, K., & Otto, T.A. (1985). Colors of monochromatic lights that vary in contrast-induced brightness. Journal of the Optical Society of America, A, 2, 76-83.

Return to Top

Chapters and Commentaries:

Otto, T. (1997). Long-term potentiation in the hippocampus of the anesthetized rat. In C.A. Paul, B. Beltz, & J. Berger-Sweeney (Eds.), Discovering Neurons.Cold Spring Harbor Laboratory Press.

Otto, T., & Eichenbaum, H. (1994). The hippocampus, long-term potentiation, and memory: Enhancing the connection. In M. Baudry & J. Davis (Eds.), Long-Term Potentiation, Vol.2. Cambridge: MIT Press (pp 305-334).

Otto, T., & Eichenbaum, H. (1992). Toward a comprehensive account of hippocampal function: Studies of olfactory learning permit an integration of data across multiple levels of neurobiological analysis. In Neuropsychology of Memory, N. Butters & L.R. Squire (Eds.). New York: Guilford (pp. 415-428).

Otto, T., & Eichenbaum, H. (1992). Olfactory learning and memory in the rat: A "model system" for studies of the neurobiology of memory. In The Science of Olfaction, K. Chobor & M. Serby, (Eds.). New York: Springer-Verlag (pp. 213-244).

Eichenbaum, H., & Otto, T. (1993). Odor-guided learning and memory in rats: Is it 'special'? Trends in Neurosciences, 16, 22-24.

Eichenbaum, H., & Otto, T. (1993). Where perception meets memory: functional coding in the hippocampus. In Brain Mechanisms of Perception and Memory: From Neuron to Behavior, T. Ono, L.R. Squire, D. Perret, & M.E. Raichle (Eds.).

Eichenbaum, H., & Otto, T. (1993). LTP and memory: Can we enhance the connection?. Trends in Neurosciences, 16, 163-164.

Eichenbaum, H., & Otto, T. (1992). The hippocampus and the sense of smell. In Chemical Signals in Vertebrates VI, R. Doty (Ed.), Plenum Press, NY. (pp. 67-77).

Eichenbaum, H., Otto, T., Wible, C., & Piper, J. (1991). Building a model of the hippocampus in olfaction and memory. In Olfaction as a Model for Computational Neuroscience, J. Davis & H. Eichenbaum, (Eds.) Cambridge: MIT Press (pp. 167-210).

Eichenbaum, H., Cohen, N.J., Otto, T., & Wible, C. (1991). Memory representation in the hippocampus: Functional domain and functional organization. In Memory: Organization and Locus of Change, L.R. Squire, G. Lynch, N.M. Weinberger, & J.L. McGaugh, (Eds). Oxford University Press.

Eichenbaum, H., Cohen, N.J., Otto, T., & Wible, C. (1991) A snapshot without the album. Brain Research Reviews, 16, 209-220.

Return to Top

Administration of Transforming Growth Factor Alpha Enhances Anatomical and Behavioral Recovery Following Olfactory Nerve Transection

Christopher D. Herzog & Tim Otto, 2002
Neuroscience, 113, 569-580

Although olfactory receptor neuron (ORN) regeneration and subsequent reinnervation of the olfactory bulb (OB) occurs following ORN injury, the intrinsic and extrinsic factors that contribute to the regulation of this dynamic process have not yet been fully identified. Recent research indicates the several growth factors (GF) have neurogenic effects on ORNs in vitro, and that chronic in vivo administration of either basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) or transforming growth factor alpha (TGF-a) following chemical lesion can enhance the normal rate of ORN reinnervation of the OB. The primary goal of the present experiments was to further assess the extent to which GF-related enhancements in the rate of anatomical recovery during ORN regeneration and reinnervation of OB are accompanied by enhancements in the normal rate of recovery of olfaction. A series of experiments was conducted to initially characterize the time course of the anatomical and behavioral recovery normally observed following ORN regeneration as a consequence of olfactory nerve transection (ONX), and to subsequently characterize the anatomical and behavioral effects of TGF-a administration on this normal rate of recovery.  Consistent with a host of prior studies, ONX produced consistent and substantial deafferentation of OB followed by a time-dependent anatomical recovery.  Subsequent experiments assessed the functional consequences of administration of TGF-a using an odor-guided behavioral task. ORN lesioned animals given injections of TGF-a during recovery were found to display enhanced conditioned responding to an olfactory stimulus compared to control ORN lesioned subjects. Further behavioral analyses suggest that this enhanced functional recovery was likely not due to non-specific effects of TGF-a on cognition or motor activity, but rather to enhanced olfactory input to the CNS. Future studies will likely reveal the exact mechanism of action mediating the anatomical and concomitant behavioral effects of this GF. Since ORNs are one of only a few populations of neurons capable of regeneration, the continued study of the cellular and molecular factors that coordinate this regenerative process may ultimately lead to the development of therapeutic strategies to promote an enhanced functional recovery following injury to other neuronal populations.

Return to Top

Return to Publications

Pavlovian Conditioning of Emotional Responses to Olfactory and Contextual Stimuli: A Potential Model for the Development and Expression of Chemical Intolerance

Tim Otto & Nicholas Giardino, 2001
Annals of the New York Academy of Sciences, 933, 291-309.

 Chemical intolerance (CI) in humans is a poorly understood phenomenon of uncertain etiology,  seemingly influenced by multiple of factors both within and between affected individuals. Several authors have suggested that the development of CI in some individuals may be due, at least in part, to Pavlovian conditioning processes in which the expression of overt symptoms to certain substances reflects classically conditioned responses to previously neutral olfactory and contextual stimuli. In this paper, we describe the potential relationship between olfactory and contextual conditioning in experimental animals and the development and expression of CI in humans. Furthermore, as significant advances have been made in delineating the brain areas that underlie these learned responses, we also review recent research on the contributions of the amygdala and perirhinal cortical region to olfactory and contextual fear conditioning.

Return to Top

Return to Publications

Patterns of Fos Expression in the Amygdala and Ventral Perirhinal Cortex Induced by Training in an Olfactory Fear Conditioning Paradigm

Luis Schettino & Tim Otto, 2001
Behavioral Neuroscience, 115(6), In Press

The activation of amygdaloid nuclei, ventral perirhinal cortex (vPRh), and several other brain areas in the rat during the acquisition and expression of olfactory fear conditioning was assessed through Fos immunocytochemistry in three separate experiments. The results of Experiment One suggest that olfactory and somatosensory inputs may functionally converge in the anterior region of the medial nucleus (aMe). The results of Experiment Two indicated that the aMe exhibited significantly greater FLI staining in animals acquiring CS-US associations than those presented with the same olfactory and somatosensory stimuli in a manner that precluded acquisition. The results of Experiment Three indicated that vPRh appeared to exhibit learning-related increases in FLI during the expression of previously acquired associations. Collectively these data suggest that the aMe and vPRh may be critically involved in different aspects of olfactory fear conditioning.

Return to Top

Return to Publications

Behavioral and Neuropsychological Foundations of Olfactory Fear Conditioning

Tim Otto, Graham Cousens, & Chris Herzog, 2000
Behavioural Brain Research, 110, 119-128

Pavlovian fear conditioning procedures have been a fruitful means of exploring the neural substrates of associative learning.  There is now substantial evidence suggesting that many aspects of conditioned fear depend critically upon the integrity of the amygdala and the perirhinal cortex. Recent studies in our laboratory examining the contributions of these areas to olfactory and contextual fear conditioning are reviewed; collectively the results of these studies suggest that the amygdala participates critically in the acquisition and expression of fear conditioned to both an olfactory CS and to the training context, while the perirhinal cortex contributes to olfactory, but not contextual, fear conditioning. Moreover, it appears that perirhinal cortex may play a prominent role in recognition of the CS following conditioning. These results are discussed in light of the extent to which they replicate and extend previous research examining the contributions of these areas to fear conditioned to auditory and visual CSs.

Return toTop

Return to Publications

Memory Representation Within the Parahippocampal Region

Brian J. Young, Tim Otto, Gregory D. Fox, & Howard Eichenbaum, 1997
Journal of Neuroscience, 17, 5183-5195

The activity of 378 single neurons was recorded from areas of the parahippocampal region (PHR), including the perirhinal and lateral entorhinal cortex, as well as the subiculum, in rats performing an odor-guided delayed nonmatching-to-sample task. Nearly every neuron fired in association with some trial event, and every identifiable trial event or behavior was encoded by neuronal activity in the PHR. The greatest proportion of cells was active during odor sampling, and for many cells, activity during this period was odor selective. In addition, odor memory coding was reflected in two general ways. First, a substantial proportion of cells showed odor-selective activity throughout or at the end of the memory delay period. Second, odor-responsive cells showed odor-selective enhancement or suppression of activity during stimulus repetition in the recognition phase of the task. These data, combined with evidence that the PHR is critical for maintaining odor memories in animals performing the same task, indicate that this cortical region mediates the encoding of specific memory cues, maintains stimulus representations, and supports specific match-nonmatch judgments critical to recognition memory. By contrast, hippocampal neurons do not demonstrate evoked or maintained stimulus-specific codings, and hippocampal damage results in little if any decrement in performance on this task. Thus it becomes increasingly clear that the parahippocampal cortex can support recognition memory independent of the distinct memory functions of the hippocampus itself.

Return to Top

Return to Publications

Neuronal Activity in the Hippocampus During Delayed Non-Match to Sample Performance in Rats: Evidence for Hippocampal Processing in Recognition Memory

Tim Otto & Howard Eichenbaum, 1992
Hippocampus, 2, 323-332

Neuronal activity in the CA1 of rats was explored with regard to functional correlates of performance in an odor-guided continuous delayed non-match to sample task. Although different CA1 cells fired in association with each identifiable trial event, these analyses focused in cells that fired selectively during the period of odor cue sampling and response generation. The firing patterns of many of these cells reflected the match or non-match comparison between current and previous odor cues independent of the particular stimuli that composed those comparisons. Such cells were more prevalent in sessions when performance was highly accurate. Hippocampal cells did not demonstrate stimulus-evoked firing that persisted through the memory delay, nor did they fire differentially to session-novel vs. Repeated odor presentations. These results suggest that the hippocampus contributes to recognition memory by processing comparisons between current information and representations of previous stored in parahippocampal and neocortical structures.

Return to Top

Return to Publications

Learning-Related Patterns of CA1 Spike Trains Parallel Stimulation Parameters Optimal for Inducing Hippocampal Long-term Potentiation

Tim Otto, Howard Eichenbaum, Sidney I. Wiener, & Cynthia G. Wible, 1991
Hippocampus, 1, 181-192

Recent studies have revealed 3 stimulation parameters that together comprise the temporal pattern of neuronal activation optimal for the induction of hippocampal LTP: high-frequency bursts, activity 100-200 ms prior to a burst, and burst delivery in phase with the ongoing hippocampal theta rhythm. The present paper reports that these 3 aspects of patterned neuronal activity, collectively referred to as "theta-bursting," are characteristic of the spike trains of CA1 pyramidal cells in rats during the sampling and analysis of learning cues in an odor discrimination task and during performances of a spatial memory task. In contrast, theta-bursting occurs relatively infrequently during behavioral events less directly related to task-relevant mnemonic processing. These findings suggest that the optimal conditions for the induction of LTP occur naturally in behaving animals, time-locked to behavioral events critical learning.

Return to Top

Return to Publications

Short-Latency Single Unit Processing in Olfactory Cortex

Jonn McCollum, John Larson, Tim Otto, Frank Schottler, Richard Granger, & Gary Lynch, 1991
Journal of Cognitive Neuroscience, 3,  293-299

Single-unit recording of layer II-III cells in olfactory (piriform) cortex was performed on awake, unrestrained rats actively engaged in learning novel odors in an olfactory discrimination task. Five of the 67 cells tested had very brief monophasic action potentials and high spontaneous firing rates (30-80 Hz); it is suggested that these units were interneurons. The remainder of the neurons had broader spikes and did not discharge for prolonged periods. Thirty-nine percent of the broad spike cells responded to at least one and usually more of the odors presented to the rats during either of the first tow trials on which that odor was present, but, in most cases, these responses occurred only very infrequently over the course of subsequent trials. Six percent of the broad-spike group, however, continued firing robustly to a single odor but not to others. From these results it appears that most cells in piriform cortex do not respond to most odors, i.e., coding is exceedingly sparse. A subgroup of the predominant broad-spike cell type does react to several odors but this response drops out with repeated exposure, perhaps because of training. However, a few members of this class (a small fraction of the total cell population) do go on responding to a particular odor, thus exhibiting a form of odor specificity. The results are discussed with regard to predictions form recently developed models of the olfactory cortex.

Return to Top

Return to Publications

Odor-Guided Fear Conditioning in Rats:1. Acquisition, Retention, and Latent Inhibition

Tim Otto, Graham Cousens, & Kimberly Rajewski, 1997
Behavioral Neuroscience, 111, 1257-1264

Three experiments examined the acquisition, retention, and latent inhibition of odor-guided fear conditioning in rats. The results of Experiment 1 indicate that forward conditioned stimulus (CS)-unconditioned stimulus (US) pairings resulted in robust freezing responses to subsequent presentation of the CS alone. In Experiment 2, rats in one group (PRE) received unreinforced preexposures to the odorant CS, and those in a second group (NON) were not preexposed to the odorant. All rats then received forward CS-US pairings. PRE rats exhibited a marked attenuation of freezing to subsequent exposure to the CS relative to NON rats. All rats were then retested at one of the following posttraining delays: 17, 24, or 31 days. Freezing behavior of the NON rats declined significantly across these delays, whereas rats in the PRE group froze no more an any delay than they had 24 hr after training. Experiment 3 examined the contextual specificity of latent inhibition. Only those rats that were preexposed and trained in the same context exhibited latent inhibition. These results indicate that odor-guided fear conditioning is a robust and useful paradigm suitable for future studies of the neural bases of associative learning.

Return to Top

Return to Publications

Odor-Guided Fear Conditioning in Rats: 2. Lesions of the Anterior Perirhinal Cortex Disrupt Fear Conditioned to the Explicit Conditioned Stimulus but Not to the Training Context

Christopher Herzog & Tim Otto, 1997
Behavioral Neuroscience, 111, 1265-1272

Previous studies examining the neural substrates of fear conditioning have indicated unequivocally that the acquisition and expression of conditioned fear depends critically on the integrity of the amygdala. The extent to which the rhinal cortical areas contribute to fear conditioned to either the explicit conditioned stimulus (CS) or to the training context is less clear, however. The effects of pretraining lesions of the anterior perirhinal (PRH) cortex on fear conditioned to an explicit odor CS and to the context in which CS-unconditioned stimulus pairing took place was examined in rats. Rats with PRH cortex lesions demonstrated a robust attenuation of fear conditioned to the explicit CS, but no attenuation of fear conditioned to the training context. These data suggest that the PRH cortex is an important component of the neural system supporting the association between olfactory cues and footshock and add to a growing body of evidence implicating the rhinal cortical regions in associative learning.

Return to Top

Return to Publications

Combined Lesions of Perirhinal and Entorhinal Cortex Impair Rats’ Performance in Two Versions of the Spatially Guided Radial-Arm Maze

Tim Otto, David Wolf, & Thomas J. Walsh, 1997
Neurobiology of Learning and Memory, 68,  21-31

The present study examined the effects of combined lesions of the entorhinal and perirhinal cortex (PRER) on performance of two versions of the spatially guided eight-arm radial maze. In the first version, all arms were baited and in each session the rats were allowed to explore the maze freely until they retrieved all of the reinforcers. PRER subjects were profoundly impaired in performance of this task, making fewer correct choices and more total errors than control subjects. In the second task, a delayed nonmatching to sample version of the radial-arm maze, each daily session was separated into two phases. In the first, predelay phase, four arms were open and the remaining four arms were blocked with clear Plexiglas barriers; subjects were permitted to visit each of the four arms and retrieve the reinforcers. In the second, postdelay phase, the subject was placed on the maze with free access to all eight of the arms, but only those arms that were blocked in the predelay phase contained reinforcers. Delays of either 10 min or 30 s separated the pre- and postdelay phases. PRER subjects were significantly impaired in their performance of this task at both delays, making fewer correct choices and more errors than controls; the magnitude of this deficit was not dependent on length of delay. These data suggest that, along with the hippocampal formation, the entorhinal and perirhinal cortices actively participate in the acquisition and performance of appetitively motivated spatial memory tasks.

Return to Top

Return to Publications

Rhinal Cortex Lesions Impair Simultaneous Olfactory Discrimination Learning in Rats

Tim Otto & David Garruto, 1997
Behavioral Neuroscience, 111, 1146-1150

Previous studies have found that combined lesions of the perirhinal and entorhinal (PRER) cortical areas do not impair, and in fact may facilitate, acquisition of successive olfactory discrimination learning. The present study sought to determine the effect of PRER lesions on the acquisition of simultaneous olfactory discrimination. Rats (N=24; 9 PRER-lesioned, 15 sham-operated controls) were trained on a single simultaneous olfactory discrimination; PRER-lesioned animals were dramatically and persistently impaired in acquisition of the discrimination relative to sham-operated subjects. These data are consistent with the view that, in concert with the hippocampus, these cortical regions participate in the encoding of relations among multiple extant stimuli.

Return to Top

Return to Publications

Entorhinal-Perirhinal Lesions Impair Performance of Rats on Two Versions of Place Learning in the Morris Water Maze

Alan H. Nagahara, Tim Otto, & Michela Gallagher, 1995
Behavioral Neuroscience, 109,  3-9

The effects of entorhinal-perirhinal lesions in rats were studied with 2 versions of a place learning task in the Morris water maze. These lesions impaired performance on a multiple-trial task (3 days of 6 trials and a probe trial). This assessment was followed by a task in which rats were repeatedly trained to find novel locations with a variable delay (30 s or 5 min) imposed between each sample trial and retention test. Entorhinal-perirhinal damage produced a delay-dependent deficit in spatial memory: Rats with lesions were impaired at the 5 min delay relative to the control group and to their own performance at 30 s. These findings are discussed in relationship to memory impairment after entorhinal damage and spatial deficits observed after hippocampal damage.

Return to Top

Return to Publications

Cognitive Decline Associated with Normal Aging in Rats: A Neuropsychological Approach

David R. Zyzak, Tim Otto, Howard Eichenbaum, & Michela Gallagher, 1995
Learning & Memory, 2, 1-16

The effects of aging on cognitive capacities were examined by comparing the performance of young and old rats on tasks characterized as dependent on different brain systems. This neuropsychological approach was employed to determine the extent to which multiple neural systems are compromised in aging and whether deterioration of one system correlates with that of another. The two tasks used in the present study were an odor-guided recognition memory task, for which different aspects of performance have been shown to be dependent on the integrity of the orbital prefrontal and perirhinal-entorhinal cortex, and the Morris water maze, for which performance depends on the medial prefrontal cortex and hippocampus. Rats were trained on the recognition memory task under minimal memory load and then challenged with longer memory delays and higher levels of inter-item interference. Considerable variation was observed in the performance of aged rats on acquisition of the recognition memory task, and unlike young rats, some aged rats could not acquire the task. Nevertheless, those aged rats who did acquire the cDNM task performed as well as young animals when the memory delay was extended and interference was elevated. In addition, consistent with previous findings, the performance of the same aged rats was highly variable in the Morris water maze task. Furthermore, although correlations between scores on the two tasks for individual aged rats that performed outside the performance range of young rats in the water maze were impaired on acquisition of the recognition memory task. This pattern of findings is consistent with age-related dysfunction in multiple subdivisions of the prefrontal cortex as well as the hippocampus and suggests that these brain regions may deteriorate in the same subgroup of aged rats.

Return to Top

Return to Publications

Two Functional Components of the Hippocampal Memory System

Howard Eichenbaum, Tim Otto, and Neal J. Cohen, 1994
Behavioral and Brain Sciences, 17,  449-518

There is considerable evidence that the hippocampal system contributes both to (1) the temporary maintenance of memories and to (2) the processing of a particular type of memory representation. The findings on amnesia suggest that these two distinguishing features of hippocampal memory processing are orthogonal. Together with anatomical and physiological data, the neuropsychological findings support a model of cortico-hippocampal interactions in which the temporal and representational properties of hippocampal memory processing are mediated separately. We propose that neocortical association areas maintain short-term memories for specific items and events prior to hippocampal processing as well as providing the final repositories of long-term memory. The parahippocampal region supports intermediate-term storage of individual items, and the hippocampal formation itself mediates an organization of memories according to relevant relationships among items. Hippocampal-cortical interactions produce (i) strong and persistent memories for events, including their constituent elements and the relationships among them, and (ii) a capacity to express memories flexibly across a wide range of circumstances.

Return to Top

Return to Publications

Complementary Roles of the Orbital Prefrontal Cortex and the Perirhinal-Entorhinal Cortices in an Odor-Guided Delayed-Nonmatching-to-Sample Task

Tim Otto & Howard Eichenbaum, 1992
Behavioral Neuroscience, 106,  762-775

Continuing efforts toward designing odor-guided tasks for rats that are similar in memory demands to tasks used typically with primates have resulted in the development of a continuous delayed-nonmatching-to-sample (cDNM) task that is guided by olfactory stimuli. The results indicate that normal subjects acquire the cDNM task rapidly and that subsequent performance deteriorates with increases in memory delay or interitem interference. Moreover, different aspects of cDNM performance were shown to be differentially sensitive to selective lesions of the orbitofrontal and parahippocampal areas. Orbitofrontal cortex lesions disproportionately impaired cDNM acquisition; delay performance was impaired only under conditions of elevated levels of interitem interference. Combined perirhinal and entorhinal cortical lesions had no effect on cDNM acquisition but impaired cDNM performance at longer delays across all levels of interference. Fornix lesions did not impair either acquisition of cDNM or subsequent performance across long delays and increased interference. This pattern of impaired and spared capacities is similar to that observed in monkeys after lesions of analogous areas and is consistent with the notion that the prefrontal cortical system contributes preferentially to learning general task "rules" such as the nonmatching rule that is inherent in cDNM, whereas the perirhinal and entorhinal cortical areas are involved in the intermediate-term maintenance of memories for specific information.

Return to Top

Return to Publications

Behavioral Tests of a Prediction from a Cortical Network Simulation

Richard Granger, Ursula Staubli, Hollie A. Powers, Tim Otto, Jose Ambros-Ingerson, & Gary Lynch, 1991
Psychological Science, 2, 116-118

Behavioral predictions arising from a simulation of olfactory paleocortex were examined using rats in an olfactory discrimination-learning task. The animals were tested to see whether, as predicted, they would recognize novel similar odors as members of a category, and whether they would nonetheless distinguish and recognize individual category members. The results were positive, providing the first evidence that rats learn perceptual clusters via unsupervised learning.

Return to Top

Return to Publications