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Biomedical subjects

Paul J Colombo

Publications and source records attributed to Paul J Colombo.

7 recordsLinked to original sources
PubMed2005

Hippocampal c-fos is necessary for long-term memory of a socially transmitted food preference.

The present article examined the requirement of hippocampal c-Fos for learning a socially transmitted food preference (STFP). We reported previously that expression of the c-Fos protein is increased in the dorsal and ventral hippocampus of rats trained on the STFP (Countryman, Orlowski, Brightwell, Oskowitz, & Colombo, 2005). Pretraining intrahippocampal antisense to the immediate early gene c-fos was administered to adult male Long-Evans rats to determine if c-fos expression is necessary for either short- or long-term memory for STFP. Guide cannulae were implanted bilaterally into the dorsal hippocampus. Antisense oligodeoxynucleotides (ODNs) were administered unilaterally either 6.5, 8.5, 10.5, or 12.5 h prior to STFP training while either sense ODNs or saline were infused into the opposite hemisphere. Immunocytochemistry was performed, and cells showing c-Fos immunoreactivity (ir) were counted from the antisense-treated hemisphere and compared to cell counts from the control hemisphere. The results indicated significant suppression of learning-induced c-Fos protein at the 8.5 and 10.5 infusion-train intervals. Additional rats were implanted with cannulae into the dorsal and ventral hippocampus, and antisense ODNs, sense ODNs, or saline were administered bilaterally 8.5h prior to training. Rats were tested immediately and 14 days after training. Rats in all groups showed a significant preference for the demonstrated food at the short-term memory test. At the long-term memory test, however, rats infused with c-fos antisense showed no preference for the demonstrated food whereas rats infused with either sense or saline maintained their preference. The present findings suggest that c-fos is necessary for consolidation of non-spatial hippocampal-dependent memory.

Animals↗
PubMed2005

CREB phosphorylation and c-Fos expression in the hippocampus of rats during acquisition and recall of a socially transmitted food preference.

In the present study, phosphorylation of cAMP-response element binding protein (pCREB) and expression of c-Fos were measured in the dorsal and ventral hippocampus, as well as in a control region, the retrosplenial cortex, of rats following acquisition and recall of a socially transmitted food preference (STFP). Behavioral analyses revealed that STFP-trained rats showed a stronger preference for the demonstrated food than did rats in social-control or odor-control conditions. Rats in a social + odor control condition displayed an intermediate preference that was not significantly different from either STFP-trained rats or the social- or odor-controls. Immunocytochemical analyses revealed increased pCREB-immunoreactivity (ir) in the ventral hippocampus of STFP-trained rats in comparisons with rats in all three control conditions and increased pCREB-ir in the dorsal hippocampus in comparisons with the social- and odor-control conditions. In contrast, c-Fos-ir was greater in the dorsal hippocampus of STFP-trained rats in comparisons with all three control conditions and greater in the ventral hippocampus than rats in the social- and odor-control conditions. Comparisons of pCREB-ir and c-Fos-ir were made also between STFP-trained rats and social-controls following either acquisition or a 48-h recall test. c-Fos-ir was greater in STFP-trained rats after both acquisition and recall, whereas pCREB was greater after recall only. There were no differences in either c-Fos-ir or pCREB-ir in comparisons between trained and control rats in the retrosplenial cortex. The current results indicate that the activity of transcription factors in the hippocampus is related to both acquisition and retention of a socially transmitted food preference.

Animals↗
PubMed2004

Learning-induced activation of transcription factors among multiple memory systems.

Experimental evidence for multiple memory systems grew initially from reports that integrity of the medial temporal lobes is necessary for some, but not all, types of memory formation. A primary inference from many studies of multiple memory systems is that they operate independently during encoding, storage, and retrieval of information. An accumulation of recent evidence, however, suggests that multiple memory systems may interact under some conditions. At the cellular level of analysis, it is accepted widely that protein synthesis is necessary for the formation of long-term memory and recent efforts have focused on the mechanisms by which learning-induced gene transcription and translation are regulated. The present review examines learning-induced activation of transcription factors among multiple memory systems. The results indicate that studies of transcriptional regulation, in conjunction with other experimental approaches, can provide complementary lines of evidence to further understanding of the extent to which multiple memory systems are independent or interactive.

Amygdala↗
PubMed2003

Cognitive strategy-specific increases in phosphorylated cAMP response element-binding protein and c-Fos in the hippocampus and dorsal striatum.

Extensive research has shown that the hippocampus and striatum have dissociable roles in memory and are necessary for "place" and "response" learning, respectively. In the present study, rats were trained on a cross maze task that could be solved by either a place or a response strategy, and the strategy used was determined by a probe trial. Phosphorylated cAMP response element-binding protein (pCREB) and c-Fos immunoreactivity (IR) were measured in the hippocampus and striatum either immediately or 1 hr after cross maze training. Immediately after training, pCREB-IR and c-Fos-IR were significantly higher in the hippocampus and striatum of trained rats than in control rats matched for motor activity, but the increase was independent of the strategy revealed at probe. One hour after training, however, pCREB-IR and c-Fos-IR were sustained in the hippocampal pyramidal and granule cell layers of place learners but returned to basal levels among response learners. In addition, pCREB-IR was sustained in the dorsomedial and dorsolateral striatum of response learners but returned to basal levels among place learners. There were no differences between place and response learners in c-Fos-IR in the striatum at either time point. The present results indicate that cross maze training causes an initial activation of transcription factors in both the hippocampus and striatum. Formation of memory for a place strategy, however, is related to sustained phosphorylation of CREB and expression of c-Fos for at least 1 hr in the hippocampus, whereas formation of memory for a response strategy is related to phosphorylation of CREB in the striatum.

Analysis of Variance↗
PubMed2002

Individual differences in spatial memory among aged rats are related to hippocampal PKCgamma immunoreactivity.

We reported previously that the extent of spatial memory impairment among aged rats was correlated positively with levels of protein kinase Cgamma in hippocampal homogenates measured by quantitative Western blotting (Colombo et al., 1997). In the current study, immunocytochemistry was used to test whether the relationship between elevated PKC-gamma and memory impairment among aged rats could be localized further within regions of the hippocampus. Six- and 24-month-old male Long-Evans rats were first trained in the water maze on a standard place-learning task and then trained 2 weeks later on a transfer task designed for rapid acquisition. In comparison with young rats, aged rats with impaired spatial memory had increased PKCgamma-immunoreactivity (PKCgamma-ir) in CA1 of the hippocampus, but not the dentate gyrus. In addition, PKCgamma-ir in CA1 was correlated positively with spatial memory impairment among aged rats on the standard place-learning and the transfer training tasks. The current results are consistent with our previous report of PKCgamma in hippocampal homogenates, and show further that the relationships between PKCgamma-ir and memory impairments among aged rats are most evident in area CA1. Thus age-related impairments of spatial memory, as well as deficits in the flexible use of previously acquired information, may result from dysregulation of PKCgamma.

Aging↗
PubMedDate not supplied

Hippocampal overexpression of mutant creb blocks long-term, but not short-term memory for a socially transmitted food preference.

Phosphorylation of the transcription factor CREB on Ser133 is implicated in the establishment of long-term memory for hippocampus-dependent tasks, including spatial learning and contextual fear conditioning. We reported previously that training on a hippocampus-dependent social transmission of food preference (STFP) task increases CREB phosphorylation in the hippocampus of trained rats in comparisons with controls. In the current study, we tested the hypothesis that CREB function is necessary for long-term memory for STFP using herpes simplex viral (HSV) vector-mediated gene transfer. Rats received intrahippocampal infusions of HSV-mCREB (a mutant form of CREB, in which Ser133 has been replaced with Ala), HSV-LacZ, or saline, and were trained 3 d later. Rats were tested for food preference (demonstrated vs. novel foods) immediately (short-term test) and 11 d (long-term test) after training. Rats in all treatment groups showed a significant preference for the demonstrated food at the short-term memory test. At the long-term memory test, however, the percentage of demonstrated food eaten by mCREB-treated rats was significantly less than that eaten by the LacZ- or saline-treated rats. Quantitative Western blotting confirmed that mCREB-infused rats had significantly more hippocampal CREB protein than controls during training. The present results show that hippocampal CREB function is necessary for long-term, but not short-term memory for STFP.

Amino Acid Substitution↗