Biomedical subjects

Tania L Roth

Publications and source records attributed to Tania L Roth.

8 recordsLinked to original sources

PubMed2006

Development switch in neural circuitry underlying odor-malaise learning.

Fetal and infant rats can learn to avoid odors paired with illness before development of brain areas supporting this learning in adults, suggesting an alternate learning circuit. Here we begin to document the transition from the infant to adult neural circuit underlying odor-malaise avoidance learning using LiCl (0.3 M; 1% of body weight, ip) and a 30-min peppermint-odor exposure. Conditioning groups included: Paired odor-LiCl, Paired odor-LiCl-Nursing, LiCl, and odor-saline. Results showed that Paired LiCl-odor conditioning induced a learned odor aversion in postnatal day (PN) 7, 12, and 23 pups. Odor-LiCl Paired Nursing induced a learned odor preference in PN7 and PN12 pups but blocked learning in PN23 pups. 14C 2-deoxyglucose (2-DG) autoradiography indicated enhanced olfactory bulb activity in PN7 and PN12 pups with odor preference and avoidance learning. The odor aversion in weanling aged (PN23) pups resulted in enhanced amygdala activity in Paired odor-LiCl pups, but not if they were nursing. Thus, the neural circuit supporting malaise-induced aversions changes over development, indicating that similar infant and adult-learned behaviors may have distinct neural circuits.

Age Factors↗

PubMed2006

Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus.

DNA (cytosine-5) methylation represents one of the most widely used mechanisms of enduring cellular memory. Stable patterns of DNA methylation are established during development, resulting in creation of persisting cellular phenotypes. There is growing evidence that the nervous system has co-opted a number of cellular mechanisms used during development to subserve the formation of long term memory. In this study, we examined the role DNA (cytosine-5) methyltransferase (DNMT) activity might play in regulating the induction of synaptic plasticity. We found that the DNA within promoters for reelin and brain-derived neurotrophic factor, genes implicated in the induction of synaptic plasticity in the adult hippocampus, exhibited rapid and dramatic changes in cytosine methylation when DNMT activity was inhibited. Moreover, zebularine and 5-aza-2-deoxycytidine, inhibitors of DNMT activity, blocked the induction of long term potentiation at Schaffer collateral synapses. Activation of protein kinase C in the hippocampus decreased reelin promoter methylation and increased DNMT3A gene expression. Interestingly, DNMT activity is required for protein kinase C-induced increases in histone H3 acetylation. Considered together, these results suggest that DNMT activity is dynamically regulated in the adult nervous system and that DNMT may play a role in regulating the induction of synaptic plasticity in the mature CNS.

Animals↗

PubMed2006

Examining the role of endogenous opioids in learned odor-stroke associations in infant rats.

Maternal touch profoundly regulates infant neural and behavioral development, and supports learned odor associations necessary for infant attachment. Endogenous opioids are well characterized to mediate the calming and analgesic properties of maternal touch; yet their role in learned odor-touch associations is unknown. We administered naltrexone, an opioid receptor antagonist, before or immediately following classical conditioning with peppermint odor and tactile stimulation (stroking) in rat neonates. Results indicate odor-stroke conditioning produces odor preferences facilitated by endogenous opioids during acquisition and memory consolidation. These results provide additional evidence for the modulatory role of opioids in neonate learning and memory. Disturbances to this system may alter the impact of touch on infant development, particularly in the realm of learning necessary for attachment.

Animals↗

PubMed2006

Signal transduction mechanisms in memory disorders.

This chapter explores some of the molecular events contributing to memory formation and how, when these events malfunction, disturbances in memory occur. After a brief discussion of signaling in the hippocampus, we will explore the topics of human mental retardation syndromes that involve disruption of these processes, including Angelman syndrome (AS), Neurofibromatosis 1 (NF1)-associated learning disorders, Coffin-Lowry syndrome (CLS), Rubinstein-Taybi syndrome (RTS), and Rett syndrome (RTT).

Animals↗

PubMed2005

Memory of early maltreatment: neonatal behavioral and neural correlates of maternal maltreatment within the context of classical conditioning.

BACKGROUND: While children form an attachment to their abusive caregiver, they are susceptible to mental illness and brain abnormalities. To understand this important clinical issue, we have developed a rat animal model of abusive attachment where odor paired with shock paradoxically produces an odor preference. Here, we extend this model to a seminaturalistic paradigm using a stressed, "abusive" mother during an odor presentation and assess the underlying learning neural circuit. METHODS: We used a classical conditioning paradigm pairing a novel odor with a stressed mother that predominantly abused pups to assess olfactory learning in a seminaturalistic environment. Additionally, we used Fos protein immunohistochemistry to assess brain areas involved in learning this pain-induced odor preference within a more controlled maltreatment environment (odor-shock conditioning). RESULTS: Odor-maternal maltreatment pairings within a seminatural setting and odor-shock pairings both resulted in paradoxical odor preferences. Learning-induced gene expression was altered in the olfactory bulb and anterior piriform cortex (part of olfactory cortex) but not the amygdala. CONCLUSIONS: Infants appear to use a unique brain circuit that optimizes learned odor preferences necessary for attachment. A fuller understanding of infant brain function may provide insight into why early maltreatment affects psychiatric well-being.

Animals↗

PubMed2003

Consolidation and expression of a shock-induced odor preference in rat pups is facilitated by opioids.

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.

Animals↗

PubMedDate not supplied

Corticosterone controls the developmental emergence of fear and amygdala function to predator odors in infant rat pups.

In many altricial species, fear responses such as freezing do not emerge until sometime later in development. In infant rats, fear to natural predator odors emerges around postnatal day (PN) 10 when infant rats begin walking. The behavioral emergence of fear is correlated with two physiological events: functional emergence of the amygdala and increasing corticosterone (CORT) levels. Here, we hypothesize that increasing corticosterone levels influence amygdala activity to permit the emergence of fear expression. We assessed the relationship between fear expression (immobility similar to freezing), amygdala function (c-fos) and the level of corticosterone in pups in response to presentation of novel male odor (predator), littermate odor and no odor. CORT levels were increased in PN8 pups (no fear, normally low CORT) by exogenous CORT (3 mg/kg) and decreased in PN12 pups (express fear, CORT levels higher) through adrenalectomy and CORT replacement. Results showed that PN8 expression of fear to a predator odor and basolateral/lateral amygdala activity could be prematurely evoked with exogenous CORT, while adrenalectomy in PN12 pups prevented both fear expression and amygdala activation. These results suggest that low neonatal CORT level serves to protect pups from responding to fear inducing stimuli and attenuate amygdala activation. This suggests that alteration of the neonatal CORT system by environmental insults such as alcohol, stress and illegal drugs, may also alter the neonatal fear system and its underlying neural control.

Amygdala↗

PubMedDate not supplied

Opioid modulation of Fos protein expression and olfactory circuitry plays a pivotal role in what neonates remember.

Paradoxically, fear conditioning (odor-0.5 mA shock) yields a learned odor preference in the neonate, presumably due to a unique learning and memory circuit that does not include apparent amygdala participation. Post-training opioid antagonism with naltrexone (NTX) blocks consolidation of this odor preference and instead yields memory of a learned odor aversion. Here we characterize the neural circuitry underlying this switch during memory consolidation. Experiment 1 assessed post-training opioid modulation of Fos protein expression within olfactory circuitry (olfactory bulb, piriform cortex, amygdala). Odor-shock conditioning with no post-training treatment (odor preference) induced significant changes in Fos protein expression in the granule cell layer of the olfactory bulb and anterior piriform cortex. Post-training opioid receptor antagonism (odor aversion) prevented the learning-induced changes in the anterior piriform cortex and also induced significant changes in Fos protein expression in the central nucleus of the amygdala. Experiment 2 assessed intra-amygdala opioid modulation of neonate memory consolidation. Post-training infusion of NTX within the amygdala permitted consolidation of an odor aversion, while vehicle-infused pups continued to demonstrate an odor preference. Overall, results demonstrate that opioids modulate memory consolidation in the neonate via modulating Fos protein expression in olfactory circuitry. Furthermore, these results suggest that opioids are instrumental in suppressing neonate fear behavior via modulating the amygdala.

Amygdala↗