Effects of suprachiasmatic nucleus lesions on habituation of the head-shake response.

Habituation is a form of non-associative learning that is characterized by a decrease in responsiveness to a repeatedly presented stimulus. A useful model of mammalian habituation is the head-shake response (HSR), a rapid twisting of the head about the anterior-to-posterior axis elicited by a stream of air to the ear. The behavioral properties of HSR habituation include sensitivity to rate of stimulus presentation and a very predictable pattern of spontaneous recovery, suggesting that a neural timing mechanism is involved. One possible candidate is the suprachiasmatic nucleus (SCN) of the hypothalamus which utilizes "clock genes" to generate daily rhythms in behavior. To test this hypothesis, the effects of SCN lesions on habituation and recovery of the HSR were assessed across four inter-session intervals (ISI: 5 min, 2, 24, and 48 h) in rats. SCN-lesioned animals showed a significant decrease in responsiveness within sessions and impaired spontaneous recovery with the 24h ISI condition. The present findings suggest that the SCN may mediate temporal patterning of spontaneous recovery from habituation and is necessary in order to appropriately reset the animal to its pre-habituation level of responsiveness.

Habituation of the head-shake response induces changes in brain matrix metalloproteinases-3 (MMP-3) and -9.

Habituation is defined as a decrease in responsiveness to a repeatedly presented stimulus. The head-shake response (HSR) demonstrates several fundamental properties of habituation including sensitivity to the frequency and intensity of stimulation, and spontaneous recovery. This response shows behavioral plasticity; however the neural plasticity presumed to underlie this behavioral phenomenon has only recently been investigated. The present study initially compared male and female rats and noted equivalent habituation and spontaneous recovery. A second experiment utilized female rats to test the hypothesis that habituation induces changes in neural plasticity. At inter-session intervals (ISIs) of 5 min, 2, 6, and 24 h following HSR habituation independent groups of rats received a second habituation experience, then tissue samples were immediately collected from hippocampal, prefrontal and piriform cortices, and cerebellum. Western blots indicated significant elevations in the expression of matrix metalloproteinase-3 (MMP-3) in hippocampal, prefrontal and piriform cortices at a delay interval of 2 h, and in the prefrontal cortex at 24 h in habituated rats. Increases in active and pro MMP-9 activity were measured by zymography in the hippocampus of habituated rats over yoked controls. Decreases in active MMP-9 activity were seen in the prefrontal cortex, and in pro MMP-9 in the piriform cortex, of habituated as compared with yoked control rats. No changes in MMP-3 or MMP-9 were observed in the cerebellum, and no changes in MMP-2 were seen in any of the four structures examined. These results suggest that habituation of the HSR produced elevations in MMP-3 expression in three of the four structures presently examined, accompanied by increased MMP-9 activity in the hippocampus and decreases in the prefrontal cortex. However, cues present in the test environment appear to have provoked elevations in MMP-3 and -9 independent of those accompanying habituation.

Role of mitogen-activated protein kinases during recovery from head-shake response habituation in rats.

Habituation is defined as a decrease in responsiveness to a repeatedly presented stimulus. The head-shake response (HSR) consists of a rapid twisting of the head about the front-to-rear axis elicited by a stream of air to the ear. This response demonstrates several fundamental properties of habituation including sensitivity to the frequency and intensity of stimulation, and spontaneous recovery. Despite an abundance of behavioral data on the HSR, relatively little is known about its physiological mechanism(s). To address this issue, changes in mitogen-activated protein kinases (MAPK) were assessed 5 min and 2, 6, and 24 h following the habituation of the HSR. Three cascades of MAPK activity were measured in the cerebellum and hippocampal, prefrontal, and piriform cortices, including extracellular-response kinase (ERK), p-38 kinase (p-38), and stress-activated protein kinase (SAPK). Significant activation of p-38 and SAPK was observed in all four brain structures, accompanied by modest changes in ERK activity. Recovery of the HSR was characterized by decreasing MAPK activation with control levels re-established 24 h after habituation. The present results suggest that MAPK activation mediates recovery from habituation; however, these findings may also support alternative interpretations such that MAPK activation reflects the encoding of spatial cues associated with the testing environment and/or are due to stress induced by the habituation protocol.

Influence of hippocampectomy on habituation, exploratory behavior, and spatial memory in rats.

Two frequently cited functions of the hippocampus are mediation of spatial memories and habituation. The present investigation employed head-shake response (HSR) as the habituated behavior in intact and bilaterally hippocampectomized rats. This HSR appears to be minimally influenced by spatial cues. These rats were further tested on two behavioral paradigms that make use of spatial cues, namely open field object exploration, and the Morris water maze. The results indicate that hippocampectomized rats revealed habituation of the HSR, but not to objects within the open field. In agreement with previous reports, hippocampectomized rats were severely impaired both in acquiring and recalling the location of the submerged platform in the Morris water maze task. In a separate experiment independent groups of rats were trained on one of these three paradigms, and tissues were collected from hippocampal, prefrontal, and piriform cortices for the measurement of matrix metalloproteinases (MMPs) as markers of neural plasticity. There were significant MMP-9 elevations in the prefrontal and piriform cortices of rats tested using the object exploration task, in the prefrontal and hippocampal cortices of rats that solved the Morris water maze task, but minimal MMP changes in any tissues taken from HSR habituated rats. These results question the hypothesis that habituation is solely mediated by the hippocampus in favor of a process that utilizes different brain structures and degrees of neural plasticity dependent upon task requirements.