Mesencephalic dopamine neurons interfacing the shell of nucleus accumbens and the dorsolateral striatum in the rat.

Parallel corticostriatonigral circuits have been proposed that separately process motor, cognitive, and emotional-motivational information. Functional integration requires that interactions exist between neurons participating in these circuits. This makes it imperative to study the complex anatomical substrate underlying corticostriatonigral circuits. It has previously been proposed that dopaminergic neurons in the ventral mesencephalon may play a role in this circuit interaction. Therefore, we studied in rats convergence of basal ganglia circuits by depositing an anterograde neuroanatomical tracer into the ventral striatum together with a retrograde fluorescent tracer ipsilaterally in the dorsolateral striatum. In the mesencephalon, using confocal microscopy, we looked for possible appositions of anterogradely labeled fibers and retrogradely labeled neurons, "enhancing" the latter via intracellular injection of Lucifer Yellow. Tyrosine hydroxylase (TH) immunofluorescence served to identify dopaminergic neurons. In neurophysiological experiments, we combined orthodromic stimulation in the medial ventral striatum with recording from ventral mesencephalic neurons characterized by antidromic stimulation from the dorsal striatum. We observed terminal fields of anterogradely labeled fibers that overlap populations of retrogradely labeled nigrostriatal cell bodies in the substantia nigra pars compacta and lateral ventral tegmental area (VTA), with numerous close appositions between boutons of anterogradely labeled fibers and nigrostriatal, TH-immunopositive neurons. Neurophysiological stimulation in the medial ventral striatum caused inhibition of dopaminergic nigrostriatal neurons projecting to the ventrolateral striatal territory. Responding nigrostriatal neurons were located in the medial substantia nigra and adjacent VTA. Our results strongly suggest a functional link between ventromedial, emotional-motivational striatum, and the sensorimotor dorsal striatum via dopaminergic nigrostriatal neurons.

Workflow and atlas system for brain-wide mapping of axonal connectivity in rat.

Detailed knowledge about the anatomical organization of axonal connections is important for understanding normal functions of brain systems and disease-related dysfunctions. Such connectivity data are typically generated in neuroanatomical tract-tracing experiments in which specific axonal connections are visualized in histological sections. Since journal publications typically only accommodate restricted data descriptions and example images, literature search is a cumbersome way to retrieve overviews of brain connectivity. To explore more efficient ways of mapping, analyzing, and sharing detailed axonal connectivity data from the rodent brain, we have implemented a workflow for data production and developed an atlas system tailored for online presentation of axonal tracing data. The system is available online through the Rodent Brain WorkBench (www.rbwb.org; Whole Brain Connectivity Atlas) and holds experimental metadata and high-resolution images of histological sections from experiments in which axonal tracers were injected in the primary somatosensory cortex. We here present the workflow and the data system, and exemplify how the online image repository can be used to map different aspects of the brain-wide connectivity of the rat primary somatosensory cortex, including not only presence of connections but also morphology, densities, and spatial organization. The accuracy of the approach is validated by comparing results generated with our system with findings reported in previous publications. The present study is a contribution to a systematic mapping of rodent brain connections and represents a starting point for further large-scale mapping efforts.

Three-dimensional organization of dendrites and local axon collaterals of shell and core medium-sized spiny projection neurons of the rat nucleus accumbens.

Medium-sized spiny projection neurons (MSN) in the head of the primate caudate nucleus are thought to have preferred dendritic orientations that tend to parallel the orientations of the striosomes. Moreover, recurrent axon collaterals of MSN in the rat dorsal striatum have been categorized into two types, i.e., restricted and widespread. The nucleus accumbens (Acb) has a highly complex compartmental organization, and the spatial organization of dendritic and axonal arbors of MSN has not yet been systematically studied. In this study, using single-cell juxtacellular labeling with neurobiotin as well as anterograde neuroanatomical tracing with biotinylated dextran amine, we investigated the three-dimensional (3D) organization of dendrites and axons of MSN of the rat Acb in relation to subregional (shell-core) and compartmental (patch-matrix) boundaries. Our results show that dendritic arbors of MSN in both the Acb shell and core subregions are preferentially oriented, i.e., they are flattened in at least one of the 3D-planes. The preferred orientations are influenced by shell-core and patch-matrix boundaries, suggesting parallel and independent processing of information. Dendritic orientations of MSN of the Acb core are more heterogeneous than those of the shell and the dorsal striatum, suggesting a more complex distribution of striatal inputs within the core. Although dendrites respect the shell-core and patch-matrix boundaries, recurrent axon collaterals may cross these boundaries. Finally, different degrees of overlap between dendritic and axonal arborizations of individual MSN were identified, suggesting various possibilities of lateral inhibitory interactions within and between, functionally distinct territories of the Acb.

Direct physiological evidence for synaptic connectivity between medium-sized spiny neurons in rat nucleus accumbens in situ.

Dual whole cell patch-clamp recordings in rat nucleus accumbens, the main component of the ventral striatum, were made to assess the presence of synaptic interconnections between medium-sized spiny neurons, a group of GABAergic and peptidergic neurons that constitute the principal cells of the striatum. Neurons were stained with biocytin for subsequent morphological analysis. Electrical activity of cells was recorded in current- and voltage-clamp mode; the characteristics of medium-sized spiny neurons were confirmed by electrophysiological and morphological properties. Thirteen of 38 medium-sized spiny neuron pairs (34%) showed a synaptic connection. In these pairs, suprathreshold stimulation with current injection evoked a train of action potentials in the presynaptic cell, which in turn elicited depolarizing postsynaptic potentials (dPSPs) in the postsynaptic cell. Twelve of these 13 pairs were connected unilaterally. The onset latency of the postsynaptic response was 1.7 +/- 0.7 ms. dPSPs were blocked by 12.5 microM bicuculline, suggesting they were mediated by GABA(A) receptors. A linear fit of the current-voltage relationship of GABAergic currents crossed the voltage axis near the value of -20 mV, in agreement with the Cl(-) equilibrium potential predicted from the composition of the artificial cerebrospinal fluid and pipette medium. No evidence for electrotonic coupling was found. Paired-pulse facilitation and depression were induced when the amplitude of the first IPSC of a pair was relatively small and large, respectively. No clear dependence of paired-pulse facilitation or depression was found on the width of the spike interval, which ranged between 100 and 380 ms. Conversely, 1- to 2-s trains of dPSPs showed marked frequency facilitation at low presynaptic frequencies, but frequency depression at high firing rates. These data show that intra-accumbens synaptic communication between medium-sized spiny neurons exists, is mediated by GABA(A) receptors, and exhibits spike train-dependent short-term dynamics.