A.B. Mulder

Short‐ and Long‐term Plasticity of the Hippocampus to Nucleus Accumbens and Prefrontal Cortex Pathways in the Rat, In Vivo

The pathways from the hippocampal formation to the nucleus accumbens and the prefrontal cortex are likely to play a role in several aspects of learning and memory. In the present study we addressed the question of how plastic changes in these structures may occur simultaneously. This question can be studied in an appropriate way in the hippocampaVfornix‐fimbria to prefrontal cortexhucleus accumbens system, since electrical stimulation of the fornix‐fimbria fibre bundle evokes characteristic field potentials in the two target areas simultaneously. First, we examined the termination field in the nucleus accumbens (medial shell and core region with an extension into the ventro‐medial caudate‐putamen) and the prefrontal cortex (deeper layers of the ventral prelimbic and ventral infralimbic areas) by recording single unit activity evoked by stimulation of fornix‐fimbria fibres in halothane anaesthetized rats. Second, we studied short‐term plasticity, namely paired pulse facilitation, in these two areas upon stimulation of the fornix‐fimbria fibres. In the nucleus accumbens, paired pulse facilitation was encountered for double pulse intervals between 25 and 500 ms, peaking around 100 ms. In the medial prefrontal cortex it was confined to intervals between 25 and 200 ms, with a peak around 75 ms. Third, we investigated whether LTP could be elicited simultaneously in the two target structures by a single tetanic stimulation (50 Hz, 2 s) of the fornix‐fimbria fibres. LTP that was sustained for more than 90 min in the medial prefrontal cortex, reached levels of 130% of control values. In the nucleus accumbens, however, only a transient form of potentiation was found which lasted no more than 60 min. These data show that synaptic weights can be changed in several target structures of the hippocampal formation, simultaneously, in a distributed way.

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 CA1/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 rostral forebrain from Ammons 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). P10 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 CA1/subiculum by a local injection of kynurenic acid. Both manipulations yielded a reversible depression of about 90% of the P25 component while P10 remained unaffected as expected. In concert a strong reduction (to 24-31%) of control values of the responses evoked in the subiculum was seen. The dynamics of the mono- and 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 P10 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 10-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.(ABSTRACT TRUNCATED AT 400 WORDS)

Hippocampal and amygdaloid interactions in the nucleus accumbens

The nucleus accumbens, in view of its afferent and efferent fiber connections, appears to hold a key position for “limbic” (e.g., hippocampal and amygdaloid) influences to reach somatomotor and autonomic brain structures, and it has therefore been considered as a limbic-motor interface. The nucleus accumbens can be subdivided into a shell and a core region, which both contain further inhomogeneities. The present account first summarizes the detailed topographical anatomical relationships of inputs from different dorso-ventral parts of the hippocampus and different rostrocaudal parts of the basal amygdaloid complex at the level of the accumbens. Subsequently, the electrophysiological characteristics of hippocampal and amygdaloid inputs in the accumbens are described. Interactions between hippocampal and amygdaloid inputs appear to exist primarily in the medial parts of both the shell and the core of the nucleus accumbens. In the short term, stimulating amygdaloid inputs appear to facilitate hippocampal throughput (heterosynaptic paired pulse facilitation), whereas stimulation of hippocampal inputs depresses amygdaloid throughput in a paired pulse paradigm. Tetanic stimulation of hippocampal inputs to the accumbens leads to a decremental long-term potentiation (LTP) of this fiber pathway (homosynaptic LTP) but, along a similar time range, to a depression of amygdaloid inputs (heterosynaptic long-term depression). The involvement of dopaminergic, GABAergic, and glutamatergic mechanisms in these interactions is discussed. Finally, it is suggested that the interactions between hippocampal and amygdaloid inputs at the level of the nucleus accumbens play a role in different aspects of associative learning.

Modifications in glutamatergic transmission after dopamine depletion of the nucleus accumbens. A combinedin vivo/in vitro electrophysiological study in the rat

The interaction between the glutamatergic and dopaminergic input in the nucleus accumbens was examined by studying the effects of dopamine depletion of the nucleus accumbens on the local field potentials, and the L-glutamate elicited responses of the nucleus accumbens in anaesthetized rats in vivo. A characteristic field potential in the nucleus accumbens is evoked by electrical stimulation of the fornix/fimbria fibres, with a monosynaptic positive peak at 10 ms (P10). Rats were unilaterally injected with 6-hydroxydopamine in the nucleus accumbens. The contralateral accumbens was sham lesioned. The rats were divided into short-term and long-term survival groups of one to two weeks and 24 weeks, respectively. In the short-term group, a striking increase (up to three times) of the amplitude of the P10 components, at the site of the lesion, compared with the sham lesioned contralateral accumbens and untreated rats, was found. The long-term group could still display a slight increase although on average this was not significantly different from controls. In the short-term group, at the centre of the lesion, the paired-pulse facilitation ratio was significantly smaller than at the more ventral, less denervated, border of the accumbens. These differences were no longer visible in the long-term group. Single-unit activity of the accumbens, elicited by the iontophoretical application of L-glutamate showed, in controls, a maximal firing frequency ranging from 5 to 40 Hz (mean 25 Hz), whereas in the short-term group more than 50% of the accumbens neurons fired with higher frequencies, reaching up to 90 Hz (mean 55 Hz). In the long-term group the firing frequency varied from 5 to 60 Hz (mean 41 Hz). No changes in threshold ejection glutamate current were found for both lesioned groups. In control rats the L-glutamate elicited responses of six cells tested could be suppressed by dopamine whereas in lesioned rats three of the six cells tested were unresponsive to dopamine. Intracellular recordings of accumbens cells in slices in 6-hydroxydopamine and sham lesioned rats, showed no significant changes in the intrinsic membrane properties, e.g. resting membrane potential, input resistance, spike threshold, action potential amplitude or duration. We conclude that dopamine denervation leads to an increase of excitability of the principal accumbens neurons. This is reflected by the increase of the firing frequency of these cells and of the amplitude of the evoked field potentials. The former is more likely of postsynaptic origin whereas the latter may also have a presynaptic contribution. These effects cannot be attributed to changes in intrinsic membrane properties of the cells.