Locomotor activity correlates with modifications of hippocampal mossy fibre synaptic transmission

Abstract

The hippocampus has long been implicated in memory formation. Although accumulating evidence suggests involvement of the hippocampus in other brain functions including locomotor regulation and emotional processes, cellular and synaptic bases underlying these functions remain largely unknown. We here report that environmental manipulations in mice unveiled the association of locomotor activity with the hippocampal mossy fibre (MF) synaptic transmission. Electrophysiological recordings of synaptic responses were made using hippocampal slices prepared from mice whose behaviour had been analysed. Environmental enrichment induced parallel decreases in open-field locomotor activity and MF synaptic facilitation. Facilitation induced by paired-pulse stimulation at relatively long intervals (>or=200 ms) was selectively reduced while the basal synaptic efficacy and high-frequency transmission were unaffected. Social isolation caused a change in behaviour in an elevated plus-maze, but neither the open-field activity nor the MF synaptic transmission was significantly altered. Effects of dopamine, a neurotransmitter essential for locomotor regulation, on the MF synapse were also examined using these mice. Environmental manipulations did not cause significant changes in potentiation of the MF synaptic transmission induced by dopamine. However, analysis of behavioural and electrophysiological results in individual subjects revealed that locomotor activity negatively correlates with magnitude of the dopamine-induced potentiation. These results suggest that the MF synapse plays important roles in the regulation of locomotor activity. We propose that the MF synapse can serve as the synaptic model for certain forms of locomotor regulation, with potential importance for investigation of the pathophysiology of psychiatric diseases using animal models.

Chronic Fluoxetine Bidirectionally Modulates Potentiating Effects of Serotonin on the Hippocampal Mossy Fiber Synaptic Transmission

“…We recently showed that the mossy fiber synaptic transmission is associated with the open-field activity (Kobayashi et al, 2006). Consistently, in the present study, we found that the chronic fluoxetine treatment modifies the open-field locomotor activity as well as the 5-HT-induced potentiation of the mossy fiber synaptic transmission.…”

Chronic Fluoxetine Selectively Upregulates Dopamine D1-Like Receptors in the Hippocampus

“…Using acute hippocampal slices, fEPSPs arising from the mossy fiber synapses were recorded. Bath-applied dopamine (10 mM) induced robust potentiation of fEPSPs (to 171 ± 7% of baseline, n ¼ 8) as in previous studies (Kobayashi et al, 2006;Kobayashi and Suzuki, 2007). In fluoxetine-treated mice (FLX), the magnitude of dopamineinduced potentiation was strongly enhanced (to 348 ± 28% of baseline, n ¼ 11, po0.001) (Figures 1a and b).…”

“…Our present results demonstrate that, in addition to these genetic factors, environmental factors can converge on this D 1 -like receptor-mediated dopaminergic modulation to regulate mossy fiber synaptic transmission. The resultant changes in potentiation of synaptic transmission by dopamine might lead to alterations of hippocampus-dependent behaviors such as locomotor activity in novel environments (Kobayashi et al, 2006). In contrast to marked upregulation of the D 1 -like ligand binding, chronic fluoxetine did not cause any increase in the 5-HT 4 ligand binding in the hippocampus.…”

“…Dopamine has been implicated in the pathophysiology of mood disorders (Suhara et al, 1992) and mechanisms of action of antidepressant drugs including SSRIs (D'Aquila et al, 2000). Dopamine can potentiate the mossy fiber synaptic transmission, and this effect is associated with activity of mice in novel environments (Kobayashi et al, 2006). The dopamine-induced synaptic potentiation at the mossy fiber synapse is mediated by D 1 -like receptors (Kobayashi and Suzuki, 2007).…”

Maternal exposure to environmental enrichment before and during gestation influences behaviour of rat offspring in a sex-specific manner

“…The hippocampus is implicated in the regulation of locomotor activity [63], moreover, exposure to EE affects the anatomy and the physiology of hippocampus [1][2][3]5,6,8,9]. It has been reported that hippocampal mossy fibre synaptic transmission plays an important role in the regulation of locomotor activity and EE induces modifications in the mossy fibre synaptic facilitation [64]. Therefore, the difference in motor activity between offspring of EE and SC mothers in the present study may result from the differential regulation of foetal hippocampal development, although the involvement of other factors is still conceivable.…”