The avian medial striatum (lobus parolfactorius, LPO) has been considered an anatomically homogeneous region. However, recent findings have indicated that somatomotor and limbic functions may be linked to anatomically distinct units. The tracer fast blue was injected into the ventral tegmental area (AVT) or substantia nigra (SN) of 1-week-old domestic chicks, and the position of retrogradely labelled neurons was mapped in striatal subregions. In another set of experiments, fast blue and red microspheres were injected into the SN and AVT, and the number and position of single- and double-labelled neurons were established. Conversely, the anterograde tracer biotinylated dextran amine was injected into different subregions of the striatum, and the position of labelled fibres and terminal fields was charted in the mesencephalic tegmentum. The neurons projecting to the SN or AVT considerably overlap in the viscerolimbic parts of the striatum, namely the medial and dorsal LPO, nucleus accumbens (Ac), tuberculum olfactorium, bed nucleus of the stria terminalis and ventral paleostriatum. Exclusive striatonigral afferents arise from the paleostriatum augmentatum and paleostriatum primitivum. Of all labelled striatal neurons, 0.22% were double-labelled from both the AVT and the SN. Thus, the AVT and SN are innervated from distinct and partially overlapping subregions of the striatum. At the cellular level, however, striatonigral and striatoventrotegmental neurons represent separate neuronal populations, even in overlapping regions. Given the arrangement of striatoventrotegmental neurons, the Ac probably does not have a distinct boundary with the LPO but extends into the anatomically defined LPO, colocalizing with medial striatal neurons.

Neural stem/progenitor cells (NSPCs) originating from the subventricular zone (SVZ) contribute to brain repair during CNS disease. The microenvironment within the SVZ stem cell niche controls NSPC fate. However, extracellular factors within the niche that trigger astrogliogenesis over neurogenesis during CNS disease are unclear. Here, we show that blood-derived fibrinogen is enriched in the SVZ niche following distant cortical brain injury in mice. Fibrinogen inhibited neuronal differentiation in SVZ and hippocampal NSPCs while promoting astrogenesis via activation of the BMP receptor signaling pathway. Genetic and pharmacologic depletion of fibrinogen reduced astrocyte formation within the SVZ after cortical injury, reducing the contribution of SVZ-derived reactive astrocytes to lesion scar formation. We propose that fibrinogen is a regulator of NSPC-derived astrogenesis from the SVZ niche via BMP receptor signaling pathway following injury.

Ca(2+)-buffer proteins (CaBPs) modulate the temporal and spatial characteristics of transient intracellular Ca(2+)-concentration changes in neurons in order to fine-tune the strength and duration of the output signal. CaBPs have been used as neurochemical markers to identify and trace neurons of several brain loci including the mammalian retina. The CaBP content of retinal neurons, however, varies between species and, thus, the results inferred from animal models cannot be utilised directly by clinical ophthalmologists. Moreover, the shortage of well-preserved human samples greatly impedes human retina studies at the cellular and network level. Our purpose has therefore been to examine the distribution of major CaBPs, including calretinin, calbindin-D28, parvalbumin and the recently discovered secretagogin in exceptionally well-preserved human retinal samples. Based on a combination of immunohistochemistry, Neurolucida tracing and Lucifer yellow injections, we have established a database in which the CaBP marker composition can be defined for morphologically identified cell types of the human retina. Hence, we describe the full CaBP make-up for a number of human retinal neurons, including HII horizontal cells, AII amacrine cells, type-1 tyrosine-hydroxylase-expressing amacrine cells and other lesser known neurons. We have also found a number of unidentified cells whose morphology remains to be characterised. We present several examples of the colocalisation of two or three CaBPs with slightly different subcellular distributions in the same cell strongly suggesting a compartment-specific division of labour of Ca(2+)-buffering by CaBPs. Our work thus provides a neurochemical framework for future ophthalmological studies and renders new information concerning the cellular and subcellular distribution of CaBPs for experimental neuroscience.

Small iontophoretic injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin were placed in the thalamic anterior dorsomedial nucleus (DMA) of domestic chicks. The projections of the DMA covered the rostrobasal forebrain, ventral paleostriatum, nucleus accumbens, septal nuclei, Wulst, hyperstriatum ventrale, neostriatal areas, archistriatal subdivisions, dorsolateral corticoid area, numerous hypothalamic nuclei, and dorsal thalamic nuclei. The rostral DMA projects preferentially on the hypothalamus, whereas the caudal part is connected mainly to the dorsal thalamus. The DMA is also connected to the periaqueductal gray, deep tectum opticum, intercollicular nucleus, ventral tegmental area, substantia nigra, locus coeruleus, dorsal lateral mesencephalic nucleus, lateral reticular formation, nucleus papillioformis, and vestibular and cranial nerve nuclei. This pattern of connectivity is likely to reflect an important role of the avian DMA in the regulation of attention and arousal, memory formation, fear responses, affective components of pain, and hormonally mediated behaviors.

To understand better the rate of neurogenesis and the distribution of new neurons in posthatch domestic chicks, we describe and compare the expression of the neuronal nuclei protein (NeuN, a.k.a. Fox-3) and doublecortin antigens in the whole brain of chicks 2 days, 8 days, and 14 weeks posthatch. In the forebrain ventricular and paraventricular zones, the density of bromodeoxyuridine-, NeuN-, and doublecortin-labeled cells was compared between chicks 24 hours and 7 days after an injection of bromodeoxyuridine (2 and 8 days posthatch, respectively). The distribution of NeuN-labeled neurons was similar to Nissl-stained tissue, with the exception of some areas where neurons did not express NeuN: cerebellar Purkinje cells and olfactory bulb mitral cells. The ventral tegmental area of 2-day-old chicks was also faintly labeled. The distribution of doublecortin was similar at all timepoints, with doublecortin-labeled profiles located throughout all forebrain areas as well as in the cerebellar granule cell layer. However, doublecortin labeling was not detectable in any midbrain or brainstem areas. Our data indicate that a significant number of new neurons is still formed in the telencephalon of posthatch domestic chicks, whereas subtelencephalic areas (except for the cerebellum) finish their neuronal expansion before hatching. Most newly formed cells in chicks leave the paraventricular zone after hatching, but a pool of neurons stays in the vicinity of the ventricular zone and matures in situ within 7 days. Proliferating cells often migrate laterally along forebrain laminae into still-developing brain areas.

Envisaged as a limbic-motor interface, the mammalian nucleus accumbens (Ac) is responsible for motivation, emotionality, and reward mechanisms. As in mammals, Ac of the domestic chick has three subdivisions: the rostral pole (AcR) lying in the rostral part of basal telencephalon, the core (AcC), corresponding to the ventromedial medial striatum, and the shell (AcS), lying ventrally and ventrolaterally to the AcC. Less well known is the connectivity of subdivisions. Here we report on the efferents of Ac subregions, using biotinylated dextran amine as anterograde tracer, deposited into the AcR, AcS, and AcC. The projections of the accumbens subregions mainly overlap in the telencephalon and the diencephalon but differ in the brainstem. In the telencephalon, the main projection sites are the ventral pallidum, the basal nucleus (Meynert), and the nucleus of the diagonal band. The lateral hypothalamus and lateral preoptic area receive strong projections from the AcR and AcS, and weaker projections from the AcC. The AcR and AcC massively innervate the subthalamic nucleus. In the brainstem the bulk of accumbens fibers were found in the compact part of the substantia nigra. All subregions project to the parabrachial region, reticular formation, periaqueductal gray, and the raphe nuclei, with some differences in the weights and subregional distributions. AcR and AcS project extensively to the ventral tegmental area, while AcC sends massive innervation to the solitary and vagal motor nuclei. Overall, the results seem to support the previously suggested distribution of Ac subregions, emphasizing similarities and differences with mammals.

Mechanisms of expression of long-term synaptic plasticity are believed to involve morphological changes of the activated synapses and remodelling of connectivity. Here, we investigated changes in synaptic and neuronal parameters in the dentate gyrus 24 h after induction of long-term potentiation (LTP) and long-term depression (LTD) in awake rats. In dentate granule cells, tetanization of the medial or lateral perforant paths induces LTP in specific synaptic bands along the dendrites in the middle and outer molecular layers, respectively, and tetanization of the lateral path induces robust LTD heterosynaptically in the middle molecular layer. This functional segregation allowed us to assess morphological changes associated with LTP and LTD in each pathway in the same population of neurons. Electron microscopy and unbiased counting methods were used to estimate neuronal density, axospinous, axodendritic and perforated synapse density, multiple synapse bouton density and postsynaptic density (PSD) area. Whereas there was no change in neuronal density, PSD area and multiple synapse boutons 24 h after either LTP or LTD, there was a noninput-specific increase in unperforated axospinous synapses after both LTP and LTD. However, we found that LTP of the medial, but not lateral, perforant path is associated with a specific increase in perforated axospinous synapses in the potentiated area. We also show that heterosynaptic LTD is associated with an input-specific increase in axodendritic synapse density. These results suggest that each perforant pathway may differ with respect to the nature of LTP-induced long-term changes and show that morphologically LTD is not simply the converse of LTP.

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