Network Path Convergence Shapes Low-Level Processing in the Visual Cortex.

Hierarchical counterstream via feedforward and feedback interactions is a major organizing principle of the cerebral cortex. The counterstream, as a topological feature of the network of cortical areas, is captured by the convergence and divergence of paths through directed links. So defined, the convergence degree (CD) reveals the reciprocal nature of forward and backward connections, and also hierarchically relevant integrative properties of areas through their inward and outward connections. We asked if topology shapes large-scale cortical functioning by studying the role of CD in network resilience and Granger causal coupling in a model of hierarchical network dynamics. Our results indicate that topological synchronizability is highly vulnerable to attacking edges based on CD, while global network efficiency depends mostly on edge betweenness, a measure of the connectedness of a link. Furthermore, similar to anatomical hierarchy determined by the laminar distribution of connections, CD highly correlated with causal coupling in feedforward gamma, and feedback alpha-beta band synchronizations in a well-studied subnetwork, including low-level visual cortical areas. In contrast, causal coupling did not correlate with edge betweenness. Considering the entire network, the CD-based hierarchy correlated well with both the anatomical and functional hierarchy for low-level areas that are far apart in the hierarchy. Conversely, in a large part of the anatomical network where hierarchical distances are small between the areas, the correlations were not significant. These findings suggest that CD-based and functional hierarchies are interrelated in low-level processing in the visual cortex. Our results are consistent with the idea that the interplay of multiple hierarchical features forms the basis of flexible functional cortical interactions.

Efficacy of weight loss intervention can be predicted based on early alterations of fMRI food cue reactivity in the striatum.

Increased fMRI food cue reactivity in obesity, i.e. higher responses to high- vs. low-calorie food images, is a promising marker of the dysregulated brain reward system underlying enhanced susceptibility to obesogenic environmental cues. Recently, it has also been shown that weight loss interventions might affect fMRI food cue reactivity and that there is a close association between the alteration of cue reactivity and the outcome of the intervention. Here we tested whether fMRI food cue reactivity could be used as a marker of diet-induced early changes of neural processing in the striatum that are predictive of the outcome of the weight loss intervention. To this end we investigated the relationship between food cue reactivity in the striatum measured one month after the onset of the weight loss program and weight changes obtained at the end of the six-month intervention. We observed a significant correlation between BMI change measured after six months and early alterations of fMRI food cue reactivity in the striatum, including the bilateral putamen, right pallidum, and left caudate. Our findings provide evidence for diet-induced early alterations of fMRI food cue reactivity in the striatum that can predict the outcome of the weight loss intervention.

Age-related and function-dependent regional alterations of free L- and D-aspartate in postembryonic chick brain.

D-aspartate (D-Asp) modulates adult neural plasticity and embryonic brain development by promoting cell proliferation, survival and differentiation. Here, developmental changes of the excitatory amino acids (EAAs) L-Glu, L-Asp and D-Asp were determined during the first postembryonic days, a time window for early learning, in selected brain regions of domestic chickens after chiral separation and capillary electrophoresis. Extracellular concentration (ECC) of EAAs was measured in microdialysis samples from freely moving chicks. ECC of D-Asp (but not L-EAAs) decreased during the first week of age, with no considerable regional or learning-related variation. ECC of L-Asp and L-Glu (but not of D-Asp) were elevated in the mSt/Ac in response to a rewarding stimulus, suggesting importance of Asp-Glu co-release in synaptic plasticity of basal ganglia. Potassium-evoked release of D-Asp, with a protracted transient, was also demonstrated. D-Asp constitutes greater percentage of total aspartate in the extracellular space than in whole tissue extracts, thus the bulk of D-Asp detected in tissue appears in the extracellular space. Conversely, only a fraction of tissue L-EAAs can be detected in extracellular space. The lack of changes in tissue D-Asp following avoidance learning indicates a tonic, rather than phasic, mechanism in the neuromodulatory action of this amino acid.

Neurotensin: revealing a novel neuromodulator circuit in the nucleus accumbens-parabrachial nucleus projection of the domestic chick.

Lower brainstem projections from nucleus accumbens (Ac) subregions to the parabrachial complex (PB), the nucleus of the solitary tract and the vagal motor nuclei have been described previously in the domestic chick by our group. Such projections, particulary those from the core and rostral pole regions of Ac have not been found in mammals or pigeons. Here we report on the presence of neurotensin (NT) in the neurons projecting from different Ac subnuclei, and also from the bed nucleus of stria terminalis, to the PB in the domestic chicken. The study is based upon correlated retrograde tracing (using Fast Blue) and NT immunohistochemistry, supplemented with regional charting and quantitative analysis of double-labeled neurons. The number of retrogradely labeled cells in Ac subdivisions reflects the size of FB tracer deposit, and the degree to which it extends to the medial PB. Of all Ac subregions, the core contained the largest amount of double-labeled cells. The findings demonstrate that the anatomical pathway through which the Ac can directly modulate taste-responsive neurons of the PB employs mainly neurotensin as a neuromodulator. The observed anatomical difference between mammals and birds is either a general taxonomic feature or it reflects feeding strategies specific for the domestic chick. The results are also relevant to a better understanding of the role of NT in food intake and reward-related behaviors in birds.

Amygdalofugal axon terminals immunoreactive for L-aspartate or L-glutamate in the nucleus accumbens of rats and domestic chickens: a comparative electron microscopic immunocytochemical study combined with anterograde pathway tracing.

Several studies have shown that L-aspartate (Asp) is present in synaptic vesicles and released exocytotically from presynaptic terminals, possibly by Ca(2+)-dependent corelease of Asp and L-glutamate (Glu). It has been demonstrated that both excitatory amino acids (EAAs) are released from the rat striatum as part of corticostriatal neurotransmission. The single or colocalized occurrence of Asp and Glu in specific synaptic boutons of the chicken medial striatum/nucl. accumbens has been demonstrated by our group using ultrastructural immunocytochemistry. However, evidence for the presence of EAAs in any specific striatal pathway was only circumstantial. Here, we report on the distribution of Asp and Glu in specific synaptic terminals of the amygdalostriatal pathway, both in rat and chicken brains, combining anterograde tracing with postembedding immunogold labeling of Asp or Glu. Immunoreactivity for Asp and Glu was observed in amygdalofugal terminals with asymmetrical synaptic junctions (morphologically representing excitatory synapses) in both species. The postsynaptic targets were either dendritic spines or small dendrites, whereas axosomatic or axo-axonic connections were not observed. Ultrastructurally, the synaptic terminals immunoreactive for Asp were indistinguishable from those immunoreactive for Glu. The findigs are consistent with an Asp-Glu corelease mechanism, with a distinct synaptic contingent, evolutionarily conserved in the amygdalostriatal pathway.

Differential changes of extracellular aspartate and glutamate in the striatum of domestic chicken evoked by high potassium or distress: an in vivo microdialysis study.

It has long been proposed that L: -aspartate (Asp) is an excitatory neurotransmitter similar to L: -glutamate (Glu) but with distinct signaling properties. The presence of Asp in excitatory synapses of the medial striatum/nucleus accumbens of domestic chicks suggests that Asp plays a role of neurotransmitter also in the avian brain. Neurotransmitters are released from the presynaptic bouton mostly by Ca(2+) dependent exocytosis. We used in vivo microdialysis to monitor the simultaneous changes of the extracellular levels of Asp and Glu in the medial striatum of young post-hatch domestic chicks. Microdialysis samples were collected from freely moving birds at 5 min intervals and analysed off-line using capillary electrophoresis. Event-related elevations of extracellular Glu and Asp concentrations in response to handling stress and to high KCl (50 mM) were observed. Increase of Glu and Asp on handling stress was 200 and 250 %, whereas on KCl stimulation the values were 300 and 1,000 %, respectively, if stress was applied before high KCl, and 150 and 200 %, respectively, in the absence of stress. In most cases, the amino acids showed correlated changes, Asp concentrations being consistently smaller at resting but exceeding Glu during stimulation. Using Ca(2+) free medium, the KCl triggered elevation of Glu was reduced. When KCl stimulation was combined with tetrodotoxin infusion, there was no significant elevation in Asp or in Glu suggesting that most of the extracellular excitatory amino acids were released by synaptic mechanisms. The results support the suggestion that Asp is co-released with Glu and may play a signaling role (as distinct from that of glutamate) in the striatum of birds.

Postnatal changes in the distribution and density of neuronal nuclei and doublecortin antigens in domestic chicks (Gallus domesticus).

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.

Efferent connections of nucleus accumbens subdivisions of the domestic chicken (Gallus domesticus): an anterograde pathway tracing study.

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.

Afferent connections of septal nuclei of the domestic chick (Gallus domesticus): a retrograde pathway tracing study.

The afferents to the septum of the domestic chicken were studied using retrograde tracers, rhodamine conjugated latex bead or Fast Blue, placed in different septal subregions. The results were verified by anterograde tracer injections deposited to selected areas. The main telencephalic afferents to the septum arise ipsilaterally from the hippocampal formation, dorsolateral corticoid area, piriform cortex, amygdaloid pallium, and the ventral pallidum. Contralateral afferents originate from the lateral septum and the amygdaloid pallium. A massive bilateral projection arises from the lateral hypothalamus. Other hypothalamic afferents arise from the periventricular, paraventricular and anterior medial nuclei, and the premammillary and mammillary areas. The dorsal thalamic nuclei (dorsal medial anterior and posterior) and the reticular dorsal nuclei also contribute septal afferents. Brainstem afferents arise bilaterally from the ventral tegmental area, substantia nigra, central gray, A8, locus coeruleus, ventral subcoeruleus nucleus, and raphe nuclei. The main terminal fields for septal afferents lie in the lateral septal nucleus and the belt of medial septal nucleus. The core of the latter is invaded mainly by fibers from the brainstem, presumably belonging to the ascending activating system. The septal afferents of the chicken are largely similar to those of other avian and nonavian species. The most prominent differences with previous pigeon data were found in the subregional selectivity of the hippocampal formation, dorsolateral corticoid area, mammillary nuclei, some dorsal thalamic nuclei, substantia nigra, and subcoeruleus nuclei in their projections to defined septal nuclei.

The organisation of the basal ganglia in the domestic chick (Gallus domesticus): anatomical localisation of DARPP-32 in relation to glutamate.

Subpallial structures are highly conserved across the different vertebrate species. They are instrumental in the neural processing relevant to adaptive learning, decision making, motivation and behavioural strategies. Of the striatal regions, our attention has been focussed on the medial and ventral striatum (MSt), now parcellated into subregions, and also including the nucleus accumbens (Ac). Similar to mammals, the avian Ac and MSt receive glutamatergic input from the pallium and dopaminergic input from the substantia nigra and ventral tegmental area. Coincidence between glutamatergic and dopaminergic synaptic activities in the ventral/medial striatum, including the Ac, is required for memory to be formed for a given pairing of stimulus and a hedonic quality or behavioural salience. The underlying mechanism involves the activation of NMDA and dopaminergic receptors, as well as the phosphorylation of dopamine-cAMP-regulated phosphoprotein (DARPP-32). Using quantitative electron microscopy of chick specimens double-labelled against glutamate and DARPP-32 we observed direct synaptic connections between glutamate immunoreactive axon terminals and DARPP-32 labelled dendrites in the MSt and also in the posterolateral telencephalon (nidopallium caudolaterale, a prefrontal cortex equivalent region) and the hippocampus. Glutamate immunoreactive axons synapsed with both DARPP-32 immunoreactive (DARPP-32+) and DARPP-32 negative (DARPP-32-) dendrites, forming asymmetrical junctions, in all brain regions observed. The existence of direct synaptic contacts between excitatory amino acid containing axon terminals and DARPP-32 containing dopaminoceptive neurons of the chicken MSt underlines the functional homology with mammalian striatal systems.

Nucleus accumbens subregions: hodological and immunohistochemical study in the domestic chick (Gallus domesticus).

The nucleus accumbens was identified in avian species some time ago. However, the precise localization and extent of this nucleus is still a matter of controversy. We have used immunolabeling against calbindin, neuropeptide Y, and DARPP-32 (dopamine- and adenosine-related phosphoprotein, 32 kDa) for the selective marking of putative accumbens subdivisions and have followed the anterograde transport of biotinylated dextran amine injected to the nucleus tractus solitarii region of 7-day-old domestic chicks. The nucleus accumbens extending between rostrocaudal atlas coordinates A 10.6 and A 8.8 can be subdivided into the core and shell, the core corresponding to the ventromedial and juxtaventricular medial striatum laterodorsal to the bed nucleus of stria terminalis, and the shell representing an arched region situated ventrally and ventrolaterally to the core. Immunoreactivity to both calbindin and neuropeptide Y is more intense in the shell than in the core division. DARPP-32 immunolabeling does not differ in the two divisions but is markedly weaker in the bed nucleus of stria terminalis, enabling the separation of this nucleus from the surrounding accumbens subdivisions. Fibers from the nucleus solitarius predominantly terminate in the shell division, similar to the situation described in mammals. Whereas the suggested core lies entirely within the boundary of the medial striatum, the shell seems partially to overlap the ventral pallidum. We have been unable to subdivide the remaining part of accumbens lying rostral to A 10.6 into a putative shell and core by the methods employed in the present study. This region probably corresponds to the rostral pole of the nucleus accumbens.

Gender-specific effect of maternal deprivation on anxiety and corticotropin-releasing hormone mRNA expression in rats.

The long-term behavioral and neurochemical effects of 24h maternal separation were assessed in rats of both genders. Maternal deprivation was applied at the age of 9 days, whereas consequences were assessed 3 months later. Deprived rats (irrespective of gender) showed a considerable growth retardation that disappeared till adulthood. The plus-maze performance of control and deprived males did not differ under normal conditions, but deprived males showed more anxiety when the test was applied shortly after stress exposure. CRH mRNA expression in the amygdala, but not in the hypothalamus, was more intense in deprived as compared with control males. Deprived females were not affected. These data suggest that (i) the maternal deprivation induced changes are larger in males than in females, (ii) maternal deprivation induces a latent behavioral disposition towards anxiety that is precipitated by acute stressors, and (iii) the changes noticed in amygdalar CRH expression may serve as mechanisms for the behavioral changes noticed.