Abstracts

Abstracts

Title:	Short- and long-term effects of various milk-delivery contingencies on sucking and nipple attachment in rat pups.
Author(s):	Brake SC ; Sullivan R ; Sager DJ ; Hofer M
Source:	Dev Psychobiol (Developmental psychobiology.) 1982 Nov; 15(6): 543-56
Abstract:	Varied milk delivery contingencies differentially affect sucking in rat pups as measured by jaw-muscle electromyographic activity. In Experiment I we found that 11-13-day-old pups sucked more frequently when receiving tiny intermittent pulses of milk than when receiving no milk, and continued to suck at a high rate for at least 30 min after cessation of milk delivery. In subsequent experiments we found that pups 13-18 days of age engaged in more frequent sucking if receiving milk continuously rather than intermittently, and that this increased rate of sucking persisted for at least 24 hr after cessation of milk delivery. Pups given experience with continuous milk delivery from 14 to 18 days of age also spent significantly more time attached to the nipple at 19 days of age than did pups in control groups. It was concluded that experience with different milk delivery schedules can affect subsequent sucking and nipple attachment behavior.

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Title:	Odor familiarity alters mitral cell response in the olfactory bulb of neonatal rats.
Author(s):	Wilson DA ; Sullivan RM ; Leon M
Source:	Brain Res (Brain research.) 1985 Oct; 354(2): 314-7
Abstract:	Previous studies have shown that rat pups have an enhanced metabolic activity to familiar odors in specific glomeruli of the olfactory bulb. The present study examined extracellularly recorded mitral cell responses to odors in this glomerular region, in odor-familiar and odor-unfamiliar pups. Mitral cells in odor-familiar pups had significantly fewer excitatory and more inhibitory responses to the familiar odor than controls. There were no differences between groups in responses to a novel odor. These results demonstrate that neonatal exposure to odors selectively alters subsequent mitral cell responsiveness to that odor.

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Title:	Early olfactory learning induces an enhanced olfactory bulb response in young rats.
Author(s):	Sullivan RM ; Leon M
Source:	Brain Res (Brain research.) 1986 Jun; 392(1-2): 278-82
Abstract:	During postnatal days 1-18, pups were simultaneously exposed to an odor and reinforcing tactile stimulation similar to that normally received from the dam. Control pups received only the odor, only the stimulation, or neither of these stimuli. On postnatal day 19, pups that had previously received simultaneous odor and tactile stimulation displayed both a behavioral odor preference and an enhanced 2-deoxyglucose uptake in specific olfactory bulb glomeruli to subsequent presentation of that odor. These results suggest that early olfactory learning enhances the neural response to odors that have acquired attractive value.

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Title:	Huddling and independent feeding of neonatal rats can be facilitated by a conditioned change in behavioral state.
Author(s):	Sullivan RM ; Brake SC ; Hofer MA ; Williams CL
Source:	Dev Psychobiol (Developmental psychobiology.) 1986 Nov; 19(6): 625-35
Abstract:	Infant rat pups were exposed to a novel odor (orange or cedar) while they received tactile stimulation (stroking of the body) or were presented with odor or stroking alone. The effects of these treatments were assessed on pups' performance in a huddling test (Experiment 1 and 2) and an independent feeding test (Experiment 3). During these tests, only pups that had received the simultaneous presentation of the odor and stroking exhibited an increase in huddling and feeding. The increase in these behaviors was dependent on the presence of the conditioned odor during testing.

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Title:	Olfactory-guided orientation in neonatal rats is enhanced by a conditioned change in behavioral state.
Author(s):	Sullivan RM ; Hofer MA ; Brake SC
Source:	Dev Psychobiol (Developmental psychobiology.) 1986 Nov; 19(6): 615-23
Abstract:	In Experiment 1, 3-6-day-old rats were simultaneously exposed to an unfamiliar odor which they will normally avoid (orange extract) and the odor of maternal saliva, or to either orange alone or saliva alone. One hour later, in a two-odor choice test, those pups which were simultaneously exposed to orange and saliva exhibited an enhanced orientation to the orange odor. In Experiment 2, orange odor was presented while pups were exposed to the odor of saliva, or while they received one of two types of tactile stimulation (stroking or tailpinching). Pups in control groups were first presented with saliva or tactile stimulation and then the orange odor. Pups that had received any of the three simultaneous exposure treatments subsequently exhibited an enhanced orientation toward the orange odor, but not the pups in the control groups. The results suggest that the tendency of neonates to avoid a novel odor can be reversed by pairing that odor with events that elicit significant increases in behavioral activity. The possibility that this phenomenon reflects a classical conditioning process is discussed.

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Title:	Single-unit analysis of postnatal olfactory learning: modified olfactory bulb output response patterns to learned attractive odors.
Author(s):	Wilson DA ; Sullivan RM ; Leon M Affiliation: Department of Psychobiology, University of California, Irvine 92717.
Source:	J Neurosci (The Journal of neuroscience : the official journal of the Society for Neuroscience.) 1987 Oct; 7(10): 3154-62
Abstract:	Neonatal rats learn to approach odors associated with stimulation normally provided by their mother. The present report describes changes in olfactory bulb single-unit activity following olfactory learning in young rats. Rat pups were exposed from postnatal day 1 to 18 to either (1) peppermint-scented air while receiving tactile stimulation (Pepp-Stroked), (2) peppermint-scented air with no tactile stimulation (Pepp-Only), (3) clean air and tactile stimulation (Stroked-Only), or (4) clean air and no tactile stimulation (Naive). On day 19, single-unit activity was recorded from mitral/tufted cells in urethane-anesthetized, freely breathing pups in response to either peppermint or a novel orange odor. Mitral/tufted cell response patterns to peppermint were significantly altered in Pepp-Stroked animals compared to control pups. Peppermint exposure alone, not associated with tactile stimulation (Pepp-Only), did not affect subsequent single-cell response patterns to that odor. In addition, the modification of response patterns was specific to peppermint and was not associated with a change in respiration rate. Furthermore, Pepp-Stroked pups had a relative behavioral preference for peppermint on day 19 compared to control pups. These results demonstrate that postnatal olfactory learning selectively modifies the subsequent response patterns of olfactory bulb output cells to the attractive odor. Furthermore, these results indicate that the initial coding of an odor's attractive value occurs within the olfactory bulb.

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Title:	One-trial olfactory learning enhances olfactory bulb responses to an appetitive conditioned odor in 7-day-old rats.
Author(s):	Sullivan RM ; Leon M Affiliation: Department of Psychobiology, University of California, Irvine 92717.
Source:	Brain Res (Brain research.) 1987 Oct; 432(2): 307-11
Abstract:	The expression of a conditioned odor preference and focal uptake of [14C]2-deoxyglucose (2-DG) within the olfactory bulb was assessed in neonatal rat pups that had undergone a single olfactory classical conditioning trial. At 6 days of age, rat pups were simultaneously exposed for 10 min to an odor (peppermint) and to a reinforcing tactile stimulation similar to that received from the dam. Three control groups received only the odor, only the stimulation, or neither of these stimuli. The next day, pups were either assessed for differential olfactory bulb activity using the 2-DG technique or tested for their olfactory preference behavior. Only pups that received simultaneous odor and tactile stimulation exhibited an attraction to the conditioned odor in the two-odor choice test. Furthermore, such pups had greater focal 2-DG uptake in the olfactory bulb glomeruli that were responsive to the odor than pups in all other groups. Thus, the olfactory bulb responds differentially to an odor which has acquired attractive value.

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Title:	Physical stimulation reduces the body temperature of infant rats.
Author(s):	Sullivan RM ; Shokrai N ; Leon M Affiliation: Department of Psychobiology, University of California, Irvine 92717.
Source:	Dev Psychobiol (Developmental psychobiology.) 1988 Apr; 21(3): 225-35
Abstract:	Physical stimulation of rat pups, of the type normally received from the mother, has been shown to regulate several behavioral and physiological systems in the young. The present paper describes a possible role of physical stimulation in an additional physiological system; the thermoregulatory system. Within a thermoneutral environment, physical stimulation produces a decrease in rectal temperature (Expt. 1). Even in an environment of increasing temperature, similar to that pups experience when in contact with the dam, physical stimulation attenuates an increase in rectal temperature (Expt. 2). The physiological mechanism of heat loss appears to involve ventilatory heat exchange resulting in convective and evaporative heat loss (Expts. 3, 4). Furthermore, physical stimulation continues to produce a decrease in rectal temperature throughout the preweanling period (Expt. 5). These results suggest that pups may not always have to resort to behavioral thermoregulatory mechanisms which require them to separate themselves from their mother. Rather, pups may be cooled, or at least a heat gain attenuated, by physical stimulation from the dam while maintaining contact with her.

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Title:	Consolidation and expression of a shock-induced odor preference in rat pups is facilitated by opioids.
Author(s):	Roth TL ; Sullivan RM Affiliation: Department of Zoology, University of Oklahoma, 73019, Norman, OK, USA
Source:	Physiol Behav (Physiology & behavior.) 2003 Jan; 78(1): 135-42
Abstract:	To support nipple attachment and huddling, rat pups must learn to approach and prefer maternal odor. Similar to other altricial species, rat pups have a sensitive period for learning this odor preference, which ends around postnatal day (PN) 10 and coincides with the emergence of walking. One characteristic of this sensitive period is that an odor paired with moderate shock elicits an odor preference. After PN10, this behavioral training produces an odor aversion, although pain threshold remains unchanged. Recently, we demonstrated that the endogenous opioid system might be a key element in the acquisition of the shock-induced odor preference during the sensitive period since antagonism of this system disrupts odor preference learning. In older pups, acquisition of a shock-induced odor aversion was unaffected by opioid system manipulation. The purpose of these experiments was to further elucidate the role of opioids in infant olfactory learning through assessment of memory consolidation and expression during and after the sensitive period. In Experiment 1, we demonstrate that naltrexone (NTX), a nonspecific opioid antagonist, given immediately following odor-shock conditioning during the sensitive period, blocks odor preference formation and yields an odor aversion. However, the same treatment does not disrupt consolidation of an odor aversion in older pups. In Experiment 2, we demonstrate that during the sensitive period, NTX disrupts expression of the shock-induced odor preference, but not the learned odor aversion in older pups. Results using this model of attachment suggest that opioids have an important role in the acquisition, consolidation, and expression of early olfactory preferences. Furthermore, since prenatal drug exposure is known to alter the endogenous opioid system, these results highlight the capacity of prenatal opiate exposure to disrupt early infant learning and attachment.

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Title:	Physical stimulation reduces the brain temperature of infant rats.
Author(s):	Sullivan RM ; Wilson DA ; Leon M Affiliation: Department of Psychobiology, University of California, Irvine 92717.
Source:	Dev Psychobiol (Developmental psychobiology.) 1988 Apr; 21(3): 237-50
Abstract:	Previous work indicated that physical stimulation, such as that which mimics the stimulation pups receive from the dam, reduces pup body temperature. The present paper reports that the body and brain temperature of 5-day-old pups covaried under steady-state thermal conditions, cold exposure, and warmth exposure (Expt. 1) suggesting that body thermoregulatory mechanisms may also regulate brain temperature. Indeed, physically stimulating pups decreased brain temperature in the neocortex (Expt. 2) and the olfactory bulb (Expt. 3). The mechanism for this brain temperature decrease appears to be an increase in ventilatory heat exchange, the same mechanism responsible for the decrease in body temperature. Pups increased respiration during stimulation, thereby increasing air flow to the lungs where convective and evaporative heat exchange occurred. Indeed, stimulating pups in a high-humidity environment blocked the decrease in brain temperature (Expt. 4). The ability of physical stimulation to decrease brain temperature appears to be limited to neonatal pups, as 10-, 15-, and 20-day-old pups did not exhibit a brain temperature decrease in response to stimulation (Expt. 5).

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Title:	Behavioral and neural correlates of postnatal olfactory conditioning: I. Effect of respiration on conditioned neural responses.
Author(s):	Sullivan RM ; Wilson DA ; Kim MH ; Leon M Affiliation: Department of Psychobiology, University of California, Irvine 92717.
Source:	Physiol Behav (Physiology & behavior.) 1988; 44(1): 85-90
Abstract:	Following olfactory classical conditioning, infant rats exhibit a preference for the conditioned odor and exhibit enhanced uptake of focal 14C 2-deoxyglucose (2-DG) within the olfactory bulb. The present experiments assessed the role of respiration on the expression of the enhanced 2-DG uptake response. Pups were conditioned from postnatal day (PN) 1-18 with an olfactory stimulus paired with a reinforcing tactile stimulus which mimics maternal contact (Odor-Stroke). Control pups received odor only or tactile stimulation only. On PN 19, pups received 1 of 3 tests: 1) a two-odor choice test, 2) an odor/2-DG test with normal respiration allowed, or 3) an odor/2-DG test with respiration experimentally controlled. The results indicated that: 1) Odor-Stroke pups learned the conditioned odor preference, 2) Odor-Stroke, normally respiring pups exhibited enhanced olfactory bulb 2-DG uptake when compared to control pups. No difference in respiration rate was detected between groups in normally respiring pups. 3) Odor Stroke pups whose breathing was experimentally controlled exhibited enhanced olfactory bulb 2-DG uptake when compared to control pups with an identical number of respirations. Together, these results demonstrate that modified respiration during testing is not required for the expression of a modified olfactory bulb response to learned attractive odors. Therefore, the data suggest that the olfactory system itself is modified by early learning.

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Title:	Norepinephrine and learning-induced plasticity in infant rat olfactory system.
Author(s):	Sullivan RM ; Wilson DA ; Leon M Affiliation: Department of Psychobiology, University of California, Irvine 92717.
Source:	J Neurosci (The Journal of neuroscience : the official journal of the Society for Neuroscience.) 1989 Nov; 9(11): 3998-4006
Abstract:	Postnatal olfactory learning produces both a conditioned behavioral response and a modified olfactory bulb neural response to the learned odor. The present report describes the role of norepinephrine (NE) on both of these learned responses in neonatal rat pups. Pups received olfactory classical conditioning training from postnatal days (PN) 1-18. Training consisted of 18 trials with an intertrial interval of 24 hr. For the experimental group, a trial consisted of a pairing of unconditioned stimulus (UCS, stroking/tactile stimulation) and the conditioned stimulus (CS, odor). Control groups received either only the CS (Odor only) or only the UCS (Stroke only). Within each training condition, pups were injected with either the NE beta-receptor agonist isoproterenol (1, 20, or 4 mg/kg), the NE beta-receptor antagonist propranolol (10, 20, 40 mg/kg), or saline 30 min prior to training. On day 20, pups received one of the following tests: (1) behavioral conditioned responding, (2) injection with 14C-2-deoxyglucose (2-DG) and exposed to the CS odor, or (3) tested for olfactory bulb mitral/tufted cell single-unit responses to the CS odor. The results indicated that training with either: (1) Odor-Stroke-Saline, (2) Odor-Stroke-Isoproterenol-Propranolol, or (3) Odor only-Isoproterenol (2 mg/kg) was sufficient to produce a learned behavioral odor preference, enhanced uptake of 14C-2-DG in the odor-specific foci within the bulb, and a modified output signal from the bulb as measured by single-cell recordings of mitral/tufted cells. Moreover, propranolol injected prior to Odor-Stroke training blocked the acquisition of both the learned behavior and olfactory bulb responses. Thus, NE is sufficient and may be necessary for the acquisition of both learned olfactory behavior and olfactory bulb responses.

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Title:	Olfactory associative conditioning in infant rats with brain stimulation as reward. I. Neurobehavioral consequences
Author(s):	Wilson, D.A. and Sullivan, R.M.
Source:	Developmental Brain Research, 1990, 53:215-221
Abstract:	In Experiment 1, infant rats were implanted with a stimulating electrode in the medial forebrain bundle/lateral hypothalamus (MFB/LH) on postnatal day 12 (PN12). Four to 6 hours later, the pups underwent associative olfactory conditioning, with half of the pups trained with 30 temporal pairings of odor (5 s) and MFB/LH stimulation (200 Hz, 300 ms), and the other half trained with random presentations of odor and MFB/LH stimulation. On PN13, pups were tested for: (1) behavioral preference for the conditioned odor; (2) focal glomerular layer 2-DG uptake to the odor; or (3) mitral/tufted cell single-unit response pattern to the odor. Odor-MFB/LH pairings produced a relative behavioral preference, enhanced focal 2-DG uptake and a modified mitral/tufted cell response pattern to the conditioned odor. Random training resulted in none of these changes. In Experiment 2, PN12 pups were anesthetized with urethane and single unit responses of mitral/tufted cells to MFB/LH stimulation were examined. MFB/LH stimulation produced a brief suppression of mitral/tufted cell activityfollowed either by a prolonged excitation(18/30 cells; 8-10 s duration) or a prolonged suppression (12/30 cells; 10-30 s). These suggest that pairing olfactory nerve input with MFB/LH stimulation modifies subsequent behavioral and physiological responses to olfactory nerve input alone. Furthermore, the prolonged olfactory bulb response to MFB/LH stimulation may be critical in this modification.

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Title:	Norepinephrine induced-plasticity and one-trial olfactory learning in neonatal rats
Author(s):	Sullivan, R.M., McGaugh, J. and Leon, M
Source:	Developmental Brain Research, 1991, 60:219-228.
Abstract:	The influence of norepinephrine (NE) on the acquisition of a conditioned odor preference and enhanced focal update of [14 C] 2-deoxyglucose (2-DG) within the olfactory bulb was assessed in neonatal rat pups. On postnatal day (PN) 6, pups were injected with either an NE receptor agonist (isoproterenol), NE receptor antagonist (propranolol or timolol), or saline before one trial odor conditioning. The experimental conditioning group received a 10-min exposure to an odor (peppermint) and reinforcing tactile stimulation similar to that received from the dam. Control groups received only the odor, only the tactile stimulation, backwards presentation of the odor and tactile stimulation or neither of these stimuli. The next day pups were either tested for an olfactory preference (Expts. 1 and 2) or assessed for differential olfactory bulb activity using the 2-DG technique (Expt. 3). The results indicate that early odor experience with either tactile stimulation or isoproterenol is sufficient to produce a learned behavioral preference and enhanced focal 2-DG uptake within the olfactory bulb. Moreover, an NE receptor blocker injected prior to training with odor and tactile stimulation blocks the acquisition of both behavioral preference and the enhanced 2-Dg uptake. In Expt. 4, the effects of tactile stimulation and isoproterenol were further assessed. An odor paired with a moderate level of either of these stimuli produce learning. However, the simultaneous presentations of a moderate level of these stimuli paired with an odor does not result in an odor preference. An odor preference maybe reinstated by simultaneous presentation of these stimuli, provided the level of these stimuli is too low to produce an odor preference when presented alone with an odor. These data suggest that exogenous NE and tactile stimulation are addictive in their effect on learning. These results are discussed in terms of the neural mechanisms underlying reinforcement in infant rats.

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Title:	The role of norepinephrine in the expression of learned olfactory neurobehavioral responses in infant rats
Author(s):	Sullivan, R.M. and Wilson, D.A.
Source:	Psychobiology, 19:308-312. (1991)
Abstract:	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 a 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.

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Title:	Modified behavioral and olfactory bulb responses to maternal odors in preweanling rats.
Author(s):	Sullivan RM ; Wilson DA ; Wong R ; Correa A ; Leon M Affiliation: Department of Psychobiology, University of California, Irvine 92717.
Source:	Brain Res Dev Brain Res (Brain research. Developmental brain research.) 1990 May 1; 53(2): 243-7
Abstract:	Rat pups acquire an attraction for maternal odors, which can vary with maternal diet. In the two experiments reported here, maternal diet was modified and both pup behavioral responses and pup olfactory bulb neural responses [( 14C]2-DG uptake) to maternal odors were examined. In experiment 1, pups were reared from birth to postnatal day 19 with either a dam fed normal rat chow or a dam fed a sucrose-based diet which suppressed her normal maternal odor. In experiment 2, pups were raised from birth to postnatal day 19 with either a dam fed the sucrose-based diet adulterated with peppermint, or the non-scented sucrose-based diet. Pups selectively expressed both a behavioral attraction and an enhanced olfactory bulb neural response to odors that they experienced in the nest.

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Title:	Olfactory classical conditioning in neonates.
Author(s):	Sullivan RM ; Taborsky-Barba S ; Mendoza R ; Itano A ; Leon M ; Cotman CW ; Payne TF ; Lott I Affiliation: Department of Pediatrics, University of California, Irvine.
Source:	Pediatrics (Pediatrics.) 1991 Apr; 87(4): 511-8
Abstract:	One-day-old, awake infants underwent an olfactory classical conditioning procedure to assess associative learning within the olfactory system of newborns. Experimental infants received ten 30-second pairings of a novel olfactory conditioned stimulus (a citrus odor of neutral value) and tactile stimulation provided by stroking as the reinforcing unconditioned stimulus (a stimulus with positive properties). Control babies received only the odor, only the stroking, or the stroking followed by the odor presentation. The next day, all infants, in either the awake or sleep state, were given five 30-second presentations of the odor. Results were analyzed from video tapes scored by an observer unaware of the infants' training condition. The results indicate that only those infants who received the forward pairings of the odor and stroking exhibited conditioned responding (head turning toward the odor) to the citrus odor. The performance of the conditioned response was not affected by the state of the baby during testing, because both awake and sleeping infants exhibited conditioned responses. Furthermore, the expression of the conditioned response was odor specific; a novel floral odor presented during testing did not elicit conditioned responses in the experimental babies. These results suggest that complex associative olfactory learning is seen in newborns within the first 48 hours of life. These baseline findings may serve as normative data against which observation from neonates at risk for neurological sequelae may be compared.

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Title:	Blockade of mitral/tufted cell habituation to odors by association with reward: A preliminary note.
Author(s):	Wilson, D.A. and Sullivan, R.M.
Source:	Brain Research, 594:143-145. (1992)
Abstract:	Association of odor and reward during the early postnatal period modifies the rat pup behavioral responses and olfactory bulb neural responses to subsequent presentations of that odor. Recent evidence has shown that olfactory bult output neurons, mitral/tufted cells, receive convergent odor and reward inputs. The present report demonstrates that contiguous odor-reward pairing 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.

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Title:	The role of olfactory bulb norepinephrine in early olfactory learning.
Author(s):	Sullivan RM ; Zyzak DR ; Skierkowski P ; Wilson DA Affiliation: Department of Psychology, University of Oklahoma, Norman 73019.
Source:	Brain Res Dev Brain Res (Brain research. Developmental brain research.) 1992 Dec 18; 70(2): 279-82
Abstract:	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.

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Title:	Role of the amygdala complex in early olfactory associative learning.
Author(s):	Sullivan RM ; Wilson DA Affiliation: Department of Psychology, University of Oklahoma, Norman 73019.
Source:	Behav Neurosci (Behavioral neuroscience.) 1993 Apr; 107(2): 254-63
Abstract:	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.

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Title:	Serotonergic influence on olfactory learning in neonatal rat
Author(s):	McLean, J.H., Darby-King, A., Sullivan, R.M. and King, S.R
Source:	Behavioral and Neural Biology, 60:152-162 (1993).
Abstract:	The role of serotonergic innervation of the olfactory bulb was examined in neonate pups (Sprague-Dawley) by utilizing an olfactory learning paradigm (Sullivan, McGaugh, & leon, 1991; Sullivan, Wilson, & Leon, 1989). One hundred fifty nanoliters of the neurotoxin 5,7-dihydroxytryptamine was injected into each anterior olfactory nucleus of postnatal Day 2 (PND 2) pups in order to selectively deplete the serotonergic (5-HT) innervation of the olfactory bulb. On PND 8, control, sham-operated, or 5-HT-depleted pups were presented with stroke (unconditioned stimulus) paired with peppermint odor (conditioned stimulus) or were presented with peppermint alone. Other pups remained naïve, i.e., they were not presented with either stroke or odor. The following day the pups were placed on a mesh screen above two boxes containing either fresh bed or bedding with peppermint odor for five 1-min trials. Control and sham-operated pups that were previously trained by the odor/stroke paradigm spent significantly more time over the peppermint odor that similarly trained 5-HT deleted pups, pups trained using the odor only paradigm or naïve pups. Immunocytochemistry verified that the 5,7-dTH injections specifically depleted the 5-HT innervation of the olfactory bulb and left the 5-HT innervation of more caudal levels of the neuraxis (e.g., pirform cortex) intact. The locomotor behavior of the pups was not affected by the 5-HT depletions. This study is the initial investigation to suggest that the 5-HT innervation to the olfactory bulb is important to the acquisition or expression of olfactory-based learned behavior in the neonate rat.

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Title:	Neural correlates of memory for odor detection conditioning in adult rats.
Author(s):	Hamrick WD ; Wilson DA ; Sullivan RM Affiliation: Department of Psychology, University of Oklahoma, Norman 73019.
Source:	Neurosci Lett (Neuroscience letters.) 1993 Nov 26; 163(1): 36-40
Abstract:	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.

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Title:	Neurobiology of associative learning in the neonate: early olfactory learning.
Author(s):	Wilson DA ; Sullivan RM Affiliation: Department of Psychology, University of Oklahoma, Norman 73019.
Source:	Behav Neural Biol (Behavioral and neural biology.) 1994 Jan; 61(1): 1-18
Abstract:	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.

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Title:	Bilateral 6-OHDA lesions of the locus coeruleus impair associative olfactory learning in newborn rats.
Author(s):	Sullivan RM ; Wilson DA ; Lemon C ; Gerhardt GA Affiliation: Department of Psychology, University of Oklahoma, Norman 73019.
Source:	Brain Res (Brain research.) 1994 Apr 18; 643(1-2): 306-9
Abstract:	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.

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Title:	The locus coeruleus, norepinephrine, and memory in newborns.
Author(s):	Sullivan RM ; Wilson DA Affiliation: Department of Zoology, University of Oklahoma, Norman 73019.
Source:	Brain Res Bull (Brain research bulletin.) 1994; 35(5-6): 467-72
Abstract:	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.

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Title:	Norepinephrine and post-training memory consolidation in neonatal rats.
Author(s):	Wilson, D.A., Pham, T. and Sullivan, R.M.
Source:	Behavioral Neuroscience, 108:1053-1058 (1994).
Abstract:	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 sessio, pups were injected with either the Norepinephrine beta-receptor antagonist propranolol or the beta-receptor agonist isoproterenol. Pups were tested 24 hrs 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 hrs. 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.

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Title:	The D2 Antagonist spiperone mimics the effects of olfactory deprivation on mitral/tufted cell odor response patterns.
Author(s):	Wilson DA ; Sullivan RM Affiliation: Department of Zoology, University of Oklahoma, Norman 73019, USA.
Source:	J Neurosci (The Journal of neuroscience : the official journal of the Society for Neuroscience.) 1995 Aug; 15(8): 5574-81
Abstract:	Wistar rats had a single nare occluded on postnatal day 30, depriving the ipsilateral olfactory bulb of odor stimulation. The deprivation lasted for either 1-2 months (short-term) or 12 months (long-term). As previously reported, deprivation greatly reduced tyrosine hydroxylase immunoreactivity (the rate limiting enzyme for dopamine synthesis) in the glomerular layer of the ipsilateral olfactory bulb. The nare was then reopened and odor response patterns of mitral/tufted cells were examined. The proportion of mitral/tufted cell single-units responding to a single odor was enhanced by deprivation. Furthermore, the proportion of mitral/tufted cells responding to more than one odor was increased by deprivation, suggesting a decrease in discrimination. Finally, in undeprived bulbs, the dopamine D2 receptor antagonist spiperone mimicked the effects of deprivation on mitral/tufted cell odor response patterns. The results are interpreted as an activity-dependent dopamine modulation of lateral and feedback inhibition in the olfactory bulb, and are compared with similar events in the dark-adapted retina.</