UvA-DARE (Digital Academic Repository) Responses of the nucleus accumbens following fornix/fimbria stimulation in the rat: identification and long-term potentiation of mono- and polysynaptic pathways

The nucleus accumbens occupies a strategic position as an interface between limbic cortex and midbrain structures involved in motor performance. The fornix-fimbria carries limbic inputs to the ventral striatum, namely by way of fibers originating in the CAl/subiculum and projecting to the nucleus accumbens. It also carries fibers arising in the septal area that project to the hippocampal formation, and projection fibers to other areas of the rostra1 forebrain from Ammon’s horn. Electrical stimulation of this bundle causes characteristic field potentials both in the nucleus accumbens and in the subiculum. In rats, under halothane anesthesia, the responses evoked by fornix/fimbria stimulation in the nucleus accumbens consist of two main positive peaks (at 10 and 25 ms, referred to as P10 and P25, respectively). PlO represents monosynaptic activation. We hypothesized that P25 reflects the activation of a polysynaptic loop, i.e. a fornix-fimbria hippocampal loop in series with the fibers that arise in the subiculum and project to the nucleus accumbens. To test this hypothesis, we reversibly blocked the fibers projecting caudally to the hippocampus by a local anesthetic (lidocaine) and the glutamatergic transmission through the CAl/subiculum by a local injection of kynurenic acid. Both manipulations yielded a reversible depression of about 90% of the P25 component while PlO remained unaffected as expected. In concert a strong reduction (to 243 1%) of control values of the responses evoked in the subiculum was seen. The dynamics of the monoand polysynaptic pathways differ markedly. The synaptic responses through both pathways are enhanced by paired-pulse stimulation, but the polysynaptic pathway is facilitated in a much stronger way. Following a tetanus (50 Hz, 2 s duration) applied to the fornix/fimbria, the PlO component of the nucleus accumbens responses showed an immediate increase by a factor of about 2 followed by a phase of gradual decrement with half-decay time of about 10 min, after which a persistent long-term potentiation of about 25% above control level was maintained for the rest of the experiment (max 90 min). The P25 component showed a transient IO-fold potentiation with return to control values after about 10 min. In contrast to the P25 elicited by a conditioning stimulus, the P25 component elicited by a second stimulus delivered at an interval of 100 ms (test stimulus) showed a persistent long-term potentiation. This suggests that in the polysynaptic pathway responsible for the P25, long-term potentiation becomes visible only after the synergistic action of the mechanisms responsible for paired-pulse facilitation and those responsible for long-term potentiation. In conclusion, the monoand polysynaptic pathways differ in the expression of induced long-term potentiation. Stimulation of the fomix/fimbria fibers also elicited a long-term potentiation of the responses of the subiculum with a time course similar to that of the PlO of the nucleus accumbens. The nucleus accumbens (Acb) receives inputs from various limbic cortical fields,’ as well as subcortical structures such as the amygdala and the limbic related thalamic nuclei.‘.2s,29 These inputs use L-Glu and/or ~-Asp as transmitter.3,6.7*26 Single cells in the Acb present increases in firing frequency following stimulation of the fornix-fimbria (Fo/Fi) or ventral subiculum in rat2*28,29 and cat.” *Present address: Sandoz Pharma Ltd., Preclinical Research, Bau 360/605, 4002 Basel, Switzerland. tTo whom correspondence should be addressed. Abbreviations: Acb, nucleus accumbens; CAl, CA3, Cornu Ammonis subfields 1 and 3, respectively; CR, conditioning response; Fo/Fi, fornix-fimbria bundle; I/O, input/ output; LTP long-term potentiation; NMDA, N-methylD-aspartate; PIO, P25, positive wave at 10 and 25 ms, respectively; PPF, paired-pulse facilitation; TR, test response. Increases in firing rate of neurons in the Acb following stimulation of the input fibers can be blocked by application within the Acb of the glutamate antagonists glutamic acid diethyl ester (in ui~o~~) or 6-cyano-7-nitroquinoxaline-2,3-dione (in vitro 18). This excitatory activation is reflected in field potentials evoked by stimulation of the Fo/Fi or of the CAl/ subiculum and recorded from the Acb. These evoked responses consist of an early positive wave with peak latency of lOms, followed by a second positive deflection with peak latency around 25 ms.* Here we denote these two positive deflections in short as PlO and P25. It was reported before’ that the distribution of spike latencies of Acb units to Fo/Fi stimulation also tends to form two clusters, around 10 and 25 ms. Previously, it was demonstrated that the short-latency PlO component represents the monosynaptic activation of the