Changes in c-fos mRNA expression in rat brain during odor discrimination learning: differential involvement of hippocampal subfields CA1 and CA3

Abstract

Levels of c-fos mRNA were measured with in situ hybridization to test for behaviorally dependent changes in neuronal activity in three subdivisions of hippocampus and in components of the olfactory and visual systems. In rats that performed a well-learned nose-poke response for water reward, c-fos mRNA levels were broadly increased, relative to values in home cage-control rats, in visual cortex, superior colliculus, olfactory bulb, and, to comparable levels, regions CA3 and CA1 of hippocampus; hybridization was not increased in the dentate gyrus. In rats first trained on the nose-poke behavior and then required to discriminate between two odors for water reward, the increase in c-fos mRNA was generally not as great and was more regionally differentiated. Thus, in olfactory bulb, hybridization was more greatly elevated in lateral than medial fields, thereby exhibiting regional activation corresponding to the topographic representation of the predominant odor sampled in the discrimination task. In hippocampus of odor-discrimination rats, c-fos mRNA levels were far greater in the region CA3 than region CA1, but remained at cage control values in stratum granulosum. Interestingly, c-fos mRNA levels in each hippocampal subdivision were highly correlated with levels in other regions (e.g., visual cortex) for home cage controls but not for rats in the two behavioral groups. Thus, c-fos mRNA levels in cage-control rats appeared to be regulated by some generalized factor acting throughout much of the brain (e.g., arousal), while odor-discrimination performance changed the pattern of expression within hippocampus, and allowed for a differentiated response by olfactory regions to emerge. These findings suggest that hippocampus possesses multiple modes of functioning and makes contributions to behavior that vary according to task demands.

Topography of Arc/Arg3.1 mRNA Expression in the Dorsal and Ventral Hippocampus Induced by Recent and Remote Spatial Memory Recall: Dissociation of CA3 and CA1 Activation

“…We also observed Arc mRNA clusters in DG (Fig. 4A) that resemble the c-fos mRNA clusters observed after performance on the odor discrimination task (Hess et al, 1995).…”

Insensitivity of the Hippocampus to Environmental Stimulation during Postnatal Development

“…Previous studies have found that hippocampal cellular discharge activity is influenced by a complex interaction of associative and contextual stimuli in the environmental (e.g., Foster et al, 1986Foster et al, , 1989Eichenbaum et al, 1989;Otto and Eichenbaum, 1992;Melia et al, 1994;Hess et al, 1995). The activity observed in these animals may be because of the processing of environmental stimuli, generalized effects of stress, or even motor activity.…”

“…The immediate early gene c-fos and its protein product Fos are considered markers of cellular activity (Dragunow and Faull, 1989;Sheng and Greenberg, 1990;Morgan and Curran, 1991;Sagar and Sharp, 1993). In the visual cortex, brief exposure to light induces a larger increase in Fos expression during the sensitive period (Rosen et al, 1992;Beaver et al, 1993;Mower, 1994); in the adult rat hippocampus, expression is induced by a number of environmental stimulations (Tischmeyer et al, 1990;Handa et al, 1993;Melia et al, 1994;Hess et al, 1995; Figure 1. Performance on the Y-maze.…”

“…In the current study, Fos immunocytochemistry and in vitro electrophysiological recording were used to measure this responsiveness in rats before and after the emergence of hippocampally dependent behavior. Environmental experience in the adult rat produces an increase in expression of the immediate early gene c-fos and its protein product Fos (Melia et al, 1994;Hess et al, 1995;Grimm and Tischmeyer, 1997) and a decrease in the expression of long-term potentiation (LTP) (Foy et al, 1987;Shors et al, 1989;Diamond et al, 1990;Shors and Thompson, 1992;Shors and Dryver, 1993;Diamond and Rose, 1994). If the immature hippocampus demonstrates increased sensitivity to environmental stimuli during this postnatal period, then the effects of environmental stimulation on these two measures should be increased before the onset of behavioral competence.…”

A Role of Fos Expression in the CA3 Region of the Hippocampus in Spatial Memory Formation in Rats

“…Some studies have suggested the importance of the CA3 region of the hippocampus in memory formation (Hess et al 1995;Gall et al 1998;Zhao et al 2000). For instance, Gall et al (1998) have demonstrated in twoodor discrimination learning that preferential activation of the CA3 region is uniquely associated with initial learning of an odor pair, whereas predominant activation of the CA1 occurred on exploration of a novel field and with overtrained animals' responding to odors.…”