Elsevier

Neuroscience

Volume 76, Issue 3, 11 December 1996, Pages 689-706
Neuroscience

The course of neural projection from the prefrontal cortex to the nucleus accumbens in the rat

https://doi.org/10.1016/S0306-4522(96)00380-6Get rights and content

Abstract

Corticostriatal neurons linking the prefrontal cortex and the nucleus accumbens connect the terminal fields of the ascending mesotelencephalic dopamine neurons and may potentially mediate cortical dopaminergic modulation of subcortical dopamine transmission. In our attempt to develop a brain slice preparation that maximally preserves this prefrontal–accumbens pathway for in vitro electrophysiological studies, knowledge of the complete course of its projection is critical.

Microinjection of biotin–dextran amine as an anterograde tracer into the prefrontal cortex revealed the following in the coronal, sagittal and oblique planes of rat brain. (1) Axonal fibers from the rostral prelimbic cortex projected at an angle of ≈60° to the horizontal plane through the infralimbic region and mainly entered the rostromedial accumbens. Some also chose a ventral route to enter the “core” of the accumbens. (2) From the central–ventral prelimbic regions, axons spread out diffusely and descended to the dorsal accumbens. They then entered throughout the rostral–caudal “shell” of the nucleus accumbens. (3) From the caudal prelimbic region of the prefrontal cortex, axonal fibers descended ≈10° to the coronal plane and entered the dorsal nucleus accumbens and the caudate nucleus. The denser caudate-projecting fibers gave rise to collaterals that entered the accumbens “core”. These results suggest that brain slices that preserve the rostral prelimbic–medial accumbens pathway can be obtained by an oblique (≈60°) cut, whereas preservation of the caudal prefrontal–accumbens neurons necessitates a 10° cut.

Finally, in whole-cell patch-clamp recordings of accumbens neurons in such slices, orthodromically evoked excitatory postsynaptic potentials to deep layer prefrontal cortical stimulation were observed, thus confirming the functional preservation of portions of this prefrontal cortex–nucleus accumbens pathway.

Section snippets

Experimental procedures

The courses of projection of corticostrital neurons from the PFC to the NAc were analysed in 12 young male Sprague–Dawley rats (University of British Columbia animal colony) weighing 90–130 g and 10 older rats weighing 250–290 g. We used both young and older adult rats because for preparing brain slices for our electrophysiological experiments, younger rats were used (90–130 g), since younger cortices appear to be less sensitive to anoxia. We also used older adult rats (250–290 g) because the

Injection sites

The deposits of BDA in the PFC created a spherical to ovoid zone, with clearly visible BDA-labeled cell bodies and dendrites of the pyramidal cells (Fig. 1). The diameter of the injected area varied from 300 to 500 μm. Most of the injections were restricted to deep layers V and VI, although injections involving both deep and superficial layers were also included in the analysis.

The deposits of BDA in the prelimbic cortex were located in: (i)the rostral part (n=5 rats), (ii) the dorsomedial part (

Methodological considerations

BDA is a useful anterograde tracer that has been shown to be readily transported over long distances and to reveal fine details of terminal structures in various species.4, 45In rats, the reported quality of terminal labeling by anterogradely transported BDA was very similar to those using Phaseolus vulgaris leucoagglutinin with upper cervical spinal cord injections. In monkeys, however, BDA injections at the upper cervical spinal cord level resulted in more widespread and dense anterograde

Summary and conclusions

Results from this study have indicated that (Fig. 12):

  • 1.

    Axonal fibers emerged from the rostral prelimbic region, spreading diversely and projecting at an angle of ≈60° to the horizontal plane, through the rostrocaudal extent of the infralimbic region, and mainly entered the rostral pole of the medial NAc. Many fibers also chose a ventral route (heavier) to enter the “core” of the NAc.

  • 2.

    Axonal fibers from the central–ventral prelimbic region fanned out from their origin and descended down directly

Acknowledgements

We are most grateful to Dr Susan Sesack of the University of Pittsburgh for her suggestions and advice in the use of the tracer biotin–dextran amine in this study. Funding for this research was provided by the British Columbia Health Research Foundation (B.C.H.R.F.) and the Medical Research Council of Canada. C.R.Y. is a B.C.H.R.F. Scholar.

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