Paired-pulse Facilitation in the Nucleus Accumbens following Stimulation of Subicular Inputs in the Rat

Anatomical tracing studies indicate that the nucleus accumbens receives inputs from limbic structures, and projects to the ventral pallidurn. In order to get more fundamental insight into how information from the limbic areas is relayed via the nucleus accumbens, electrophysiological experiments were carried out in rats under halothane anaesthesia. Inputs originating in the subiculum were activated by electrical stimulation of the fomix fibres, and both field potentials and extracellular unit activity were recorded from the medial and lateral aspects of the nucleus accumbens. Evoked potentials consisted of two positive peaks (Pl at 10 ms and P2 at 25-30 ms). In between a negative-going wave (Nl) was present. These initial components were followed by a complex negative wave (N2) with variable duration of 3(rlOOms. The P2 and N2 components showed a conspicuous paired-pulse facilitation at stimulus intervals between 80 and at least 200 ms. When responses were recorded at increasing stimulus intensity, the second response emerged at lower threshold than the first response. The mechanisms underlying these phenomena were investigated by analysing the extracellularly recorded unit activity. Primarily, excitatory responses were found. Onset-latencies could be divided roughly into two clusters, one around IOms, representing monosynaptic inputs, and a second around 24-26 ms. Inhibitory responses were also found. Stimulation of the vental pallidurn was carried out in order to test whether the cells that could be driven by stimulation of the subicular inputs were projection cells. Latencies of antidromic action potentials ranged from 9 to 13 ms. A minority of the identified projection cells were activated by limbic inputs. The projection cells were found in the core region of the nucleus accumbens. Units that were inhibited by stimulation of the limbic inputs were found in the shell only, whereas excitatory responses were measured in both subdivisions of the nucleus accumbens. For the latter responses a significant enhancement, by a factor of four, was found using double pulse stimulation of the fornix at intervals of 1OOms. The basic el~trophysiolo~cal properties are compared with those described in the literature, and speculations about the possible mechanisms responsible for the paired-pulse facilitation phenomena are put forward. The nucleus accumbens (Acb) receives inputs from various limbic structures, namely the subiculum and other limbic cortical fields,” the amygdala” and the limbic related thalamic nuclei.’ The Acb also receives inputs from the midbrain dopaminergic cell groups (i.e. ventral tegmental area, VIA). It projects to the substantia nigra pars reticulata and dopaminergic cell groups Ag, A9 and A10 (VTA). It has been known for a long time that the Acb projects to the ventral pallidurn’) (VP) and subpallidal areas.” The output fibres are mainly GABAergic and thus may exert an inhibitory influence on target neurons. In order to understand how limbic influences are mediated through the Acb to more caudally lying areas, it is of importance to know how the limbic inputs affect Acb output neurons. Here we describe experiments carried out to clarify how inputs arising from the hippocampal forrrmtion affect the neuronal networks of the Acb in vim Yang and Mogenson” reported excitatory responses in a large number of units in the medial Acb following stimulation of the ventral subiculum, 37% of which could be identified as projection cells to either VP or subpallidal areas. Thus, 63% of the excitatory responses were recorded from unidentified cells. Inhibitory responses following subicular or fornix stimulation have also been reported.6s26 However, the balance between excitatory and inhibitory action is, as yet, not well documented. De France et al.’ investigated a possible interaction between successive responses using paired-pulse stimulation with intervals in the range of 10-40 ms. They showed that the response to the second, or test stimulus was suppressed at intervals below 30 ms. In a separate paper6 these authors reported a suppressive effect of dopamine on the responses when the input fibres were stimulated once everv 1-2 s. For Abbreviatims: Acb, nucleus accumbens; fo/fI, fomixfimbria bundle; IS/SD, initial segment/somatodendritic; stimulation with a rate of 6 pulses/s (intervals 167 ms) NMDA, N-methyl-n-aspartate; PSTH, p&stimulus no such effect was observed. time histograms; Sub,,“, subiculum, dorsal resp. ventral These experimental findings led us to formulate the portion; VP, ventral or subcommissural pallidurn; VTA, hypothesis that the transmission of signals through ventral tegmental area. the neuronal networks of the Acb may take place in