European Journal of Neuroscience (Eur J Neurosci)

Publications in this journal

• Article: Corticotropin-releasing factor infusion into nucleus incertus suppresses medial prefrontal cortical activity and hippocampo-medial prefrontal cortical long-term potentiation.

  Usman Farooq, Ramamoorthy Rajkumar, Shalini Sukumaran, You Wu, Wei Hao Tan, Gavin Stewart Dawe
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  ABSTRACT: The medial prefrontal cortex (mPFC) in the rat has been implicated in a variety of cognitive processes, including working memory and expression of fear memory. We investigated the inputs from a brain stem nucleus, the nucleus incertus (NI), to the prelimbic area of the mPFC. This nucleus strongly expresses corticotropin-releasing factor type 1 (CRF1 ) receptors and responds to stress. A retrograde tracer was used to verify connections from the NI to the mPFC. Retrogradely labelled cells in the NI expressed CRF receptors. Electrophysiological manipulation of the NI revealed that stimulation of the NI inhibited spontaneous neuronal firing in the mPFC. Similarly, CRF infusion into the NI, in order to mimic a stressful condition, inhibited neuronal firing and burst firing in the mPFC. The effect of concurrent high-frequency stimulation of the NI on plasticity in the hippocampo-prelimbic medial prefrontal cortical (HP-mPFC) pathway was studied. It was found that electrical stimulation of the NI impaired long-term potentiation in the HP-mPFC pathway. Furthermore, CRF infusion into the NI produced similar results. These findings might account for some of the extra-pituitary functions of CRF and indicate that the NI may play a role in stress-driven modulation of working memory and possibly other cognitive processes subserved by the mPFC.
  European Journal of Neuroscience 05/2013;
• Article: Effects of regularity on the processing of sound omission in a tone sequence in musicians and non-musicians.

  Kentaro Ono, Masao Matsuhashi, Tatsuya Mima, Hidenao Fukuyama, Christian F Altmann
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  ABSTRACT: Numerous studies have reported that perceptual grouping affects the pre-attentive processing of sound omission in a sequence of tones. However, it remains unclear whether or not the perceptual grouping and musical experience affect the attentive processing of sound omission. To this end, we created a sequence of loud (L) and soft (S) tones grouped as 'LLSLLS…' and a random sequence of the L and S tones. The omission of the L tones was inserted pseudo-randomly in the random sequence, and there were two positions at which it was inserted. For within-group omission, the omission was after the first L tone within the 'LLS' pattern. For between-group omission, the omission was inserted between the patterns. The brain response to the omission in musicians and non-musicians was measured using magnetoencephalography. During the magnetoencephalography measurement, the subjects' performance in a task to detect the omission was faster in the random sequence than in the group sequence. Source analysis showed that the omission in the random sequence caused greater activity than that in the group sequence. The increase was found in the right inferior parietal lobe in musicians, whereas it was found in the left superior temporal gyrus in non-musicians. These results suggest that the attentive processing of perceptual grouping might implicate the left superior temporal gyrus or right inferior parietal lobe, depending on musical experience.
  European Journal of Neuroscience 05/2013;
• Article: NMDA receptors in the lateral hypothalamus have an inhibitory influence on the tachycardiac response to acute restraint stress in rats.

  Milena V Deolindo, Daniel G Reis, Carlos C Crestani, Rodrigo F Tavares, Leonardo B M Resstel, Fernando M A Corrêa
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  ABSTRACT: The aim of the present study was to investigate the role of the lateral hypothalamus (LH) and its local glutamatergic neurotransmission in the cardiovascular adjustments observed when rats are submitted to acute restraint stress. Bilateral microinjection of the nonspecific synaptic inhibitor CoCl2 (0.1 nmol in 100 nL) into the LH enhanced the heart rate (HR) increase evoked by restraint stress without affecting the blood pressure increase. Local microinjection of the selective N-methyl-d-aspartate (NMDA) glutamate receptor antagonist LY235959 (2 nmol in 100 nL) into the LH caused effects that were similar to those of CoCl2 . No changes were observed in the restraint-related cardiovascular response after a local microinjection of the selective non-NMDA glutamatergic receptor antagonist NBQX (2 nmol in 100 nL) into the LH. Intravenous administration of the muscarinic cholinergic receptor antagonist homatropine methyl bromide (0.2 mg/kg), a quaternary ammonium drug that does not cross the blood-brain barrier, abolished the changes in cardiovascular responses to restraint stress following LH treatment with LY235959. In summary, our findings show that the LH plays an inhibitory role on the HR increase evoked by restraint stress. Present results also indicate that local NMDA glutamate receptors, through facilitation of cardiac parasympathetic activity, mediate the LH inhibitory influence on the cardiac response to acute restraint stress.
  European Journal of Neuroscience 05/2013;
• Article: Cognitive regulation of saccadic velocity by reward prospect.

  Lewis L Chen, Leroy Y Hung, Julie Quinet, Kevin Kosek
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  ABSTRACT: It is known that expectation of reward speeds up saccades. Past studies have also shown the presence of a saccadic velocity bias in the orbit, resulting from a biomechanical regulation over varying eccentricities. Nevertheless, whether and how reward expectation interacts with the biomechanical regulation of saccadic velocities over varying eccentricities remains unknown. We addressed this question by conducting a visually guided double-step saccade task. The role of reward expectation was tested in monkeys performing two consecutive horizontal saccades, one associated with reward prospect and the other not. To adequately assess saccadic velocity and avoid adaptation, we systematically varied initial eye positions, saccadic directions and amplitudes. Our results confirmed the existence of a velocity bias in the orbit, i.e., saccadic peak velocity decreased linearly as the initial eye position deviated in the direction of the saccade. The slope of this bias increased as saccadic amplitudes increased. Nevertheless, reward prospect facilitated velocity to a greater extent for saccades away from than for saccades toward the orbital centre, rendering an overall reduction in the velocity bias. The rate (slope) and magnitude (intercept) of reward modulation over this velocity bias were linearly correlated with amplitudes, similar to the amplitude-modulated velocity bias without reward prospect, which presumably resulted from a biomechanical regulation. Small-amplitude (≤ 5°) saccades received little modulation. These findings together suggest that reward expectation modulated saccadic velocity not as an additive signal but as a facilitating mechanism that interacted with the biomechanical regulation.
  European Journal of Neuroscience 05/2013;
• Article: Rostroventrolateral medulla neurons with commissural projections provide input to sympathetic premotor neurons: anatomical and functional evidence.

  Anita Turner, Natasha Kumar, Melissa Farnham, Mandy Lung, Paul Pilowsky, Simon McMullan
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  ABSTRACT: The activity of neurons in the rostral ventrolateral medulla (RVLM) is critical for the generation of vasomotor sympathetic tone. Multiple pre-sympathetic pathways converge on spinally projecting RVLM neurons, but the origin and circumstances in which such inputs are active are poorly understood. We have previously shown that input from the contralateral brainstem contributes to the baseline activity of this population: in the current study we investigate the distribution, phenotype and functional properties of RVLM neurons with commissural projections in the rat. We firstly used retrograde transport of fluorescent microspheres to identify neurons that project to the contralateral RVLM. Labelled neurons were prominent in a longitudinal column that extended over 1 mm caudal from the facial nucleus and contained hybridisation products indicating enkephalin (27%), GABA (15%) and adrenaline (3%) synthesis and included 6% of bulbospinal neurons identified by transport of cholera toxin B. Anterograde transport of fluorescent dextran-conjugate from the contralateral RVLM revealed extensive inputs throughout the RVLM that frequently terminated in close apposition with catecholaminergic and bulbospinal neurons. In urethane-anaesthetised rats we verified that 28/37 neurons antidromically activated by electrical stimulation of the contralateral pressor region were spontaneously active, of which 13 had activity locked to central respiratory drive and 15 displayed ongoing tonic discharge. In six tonically active neurons sympathoexcitatory roles were indicated by spike-triggered averages of splanchnic sympathetic nerve activity. We conclude that neurons in the RVLM project to the contralateral brainstem, form synapses with sympathetic premotor neurons, and have functional properties consistent with sympthoexcitatory function.
  European Journal of Neuroscience 05/2013;
• Article: Cellular and molecular mechanisms controlling the migration of neocortical interneurons.

  Oscar Marín
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  ABSTRACT: The discovery, approximately 15 years ago, that cortical GABAergic interneurons originate outside the pallium has revolutionized our understanding of the development of the cerebral cortex. It is now clear that glutamatergic pyramidal cells and GABAergic interneurons follow largely distinct development programs, a notion that has challenged our views on how these neurons assemble to form precise neural circuits. In this review, I summarize our current knowledge of the mechanisms that control the migration of neocortical interneurons, a process that can be subdivided into three consecutive phases: migration to the cortex, intracortical dispersion, and layering.
  European Journal of Neuroscience 05/2013;
• Article: Persistent firing supported by an intrinsic cellular mechanism in hippocampal CA3 pyramidal cells.

  Arthur Jochems, Motoharu Yoshida
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  ABSTRACT: Short-term information retention is crucial for information processing in the brain. It has long been suggested that the hippocampal CA3 region is able to support short-term information retention through persistent neural firing. Theoretical studies have shown that this persistent firing can be supported by abundant excitatory recurrent connections in CA3. However, it remains unclear whether individual cells can support persistent firing. In this study, using in vitro whole-cell patch-clamp recordings in a rat hippocampal slice preparation, we show that hippocampal CA3 pyramidal cells support persistent firing under perfusion of the cholinergic agonist carbachol (10 μm). Furthermore, in contrast to earlier theoretical studies, this persistent firing is independent of ionotropic glutamatergic synaptic transmission and is supported by the calcium-activated non-selective cationic current. Because cholinergic receptor activation is crucial for short-term memory tasks, persistent firing in individual cells may support short-term information retention in the hippocampal CA3 region.
  European Journal of Neuroscience 05/2013;
• Article: The orbitofrontal cortex regulates outcome-based decision-making via the lateral striatum.

  Shannon L Gourley, Anastasia Olevska, Kelsey S Zimmermann, Kerry J Ressler, Ralph J Dileone, Jane R Taylor
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  ABSTRACT: The orbitofrontal cortex (oPFC) sends substantial projections to the ventrolateral striatum and aspects of the nucleus accumbens that are, functionally, poorly understood. This is despite probable cortico-striatal involvement in multiple diseases such as addiction and obsessive-compulsive disorder. Here we surgically disconnected the oPFC from the ventrolateral striatum using unilateral asymmetric lesions in mice and classified instrumental decision-making strategies. Mice with symmetric lesions that spared one oPFC-striatal network served as controls. As a complementary approach, we selectively knocked down Brain-derived neurotrophic factor (Bdnf) bilaterally in the oPFC and ascertained behavioral and neurobiological consequences within the downstream striatum. oPFC-striatal disconnection and oPFC Bdnf knockdown blocked sensitivity to outcome-predictive relationships in both food-reinforced and cocaine-associated settings. Bdnf knockdown simultaneously regulated striatal BDNF expression, and striatal c-Fos predicted sensitivity to action-outcome associative contingencies. Previous evidence strongly implicates the dorsolateral striatum in stimulus-response habit formation. Our findings thus provide novel evidence for functional compartmentalisation within the lateral striatum, with the dorsal compartment subserving classical stimulus-response habit systems and a ventral compartment coordinating outcome-based decision-making via oPFC interactions. This compartmentalisation may apply to both 'natural', as in the case of food-reinforced behavior, and 'pathological', as in the case of cocaine-seeking, contexts.
  European Journal of Neuroscience 05/2013;
• Article: Sleep: a synchrony of cell activity-driven small network states.

  James M Krueger, Yanhua H Huang, David M Rector, Daniel J Buysse
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  ABSTRACT: We posit a bottom-up sleep-regulatory paradigm in which state changes are initiated within small networks as a consequence of local cell activity. Bottom-up regulatory mechanisms are prevalent throughout nature, occurring in vastly different systems and levels of organization. Synchronization of state without top-down regulation is a fundamental property of large collections of small semi-autonomous entities. We posit that such synchronization mechanisms are sufficient and necessary for whole-organism sleep onset. Within the brain we posit that small networks of highly interconnected neurons and glia, for example cortical columns, are semi-autonomous units oscillating between sleep-like and wake-like states. We review evidence showing that cells, small networks and regional areas of the brain share sleep-like properties with whole-animal sleep. A testable hypothesis focused on how sleep is initiated within local networks is presented. We posit that the release of cell activity-dependent molecules, such as ATP and nitric oxide, into the extracellular space initiates state changes within the local networks where they are produced. We review mechanisms of ATP induction of sleep-regulatory substances and their actions on receptor trafficking. Finally, we provide an example of how such local metabolic and state changes provide mechanistic explanations for clinical conditions, such as insomnia.
  European Journal of Neuroscience 05/2013;
• Article: Inhibition of protein kinase A activity depresses phrenic drive and glycinergic signalling, but not rhythmogenesis in anaesthetized rat.

  P G R Burke, L O Sousa, V J Tallapragada, A K Goodchild
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  ABSTRACT: The cAMP-protein kinase A (PKA) pathway plays a critical role in regulating neuronal activity. Yet, how PKA signalling shapes the population activity of neurons that regulate respiratory rhythm and motor patterns in vivo is poorly defined. We determined the respiratory effects of focally inhibiting endogenous PKA activity in defined classes of respiratory neurons in the ventrolateral medulla and spinal cord by microinjection of the membrane-permeable PKA inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS) in urethane-anaesthetized adult Sprague Dawley rats. Phrenic nerve activity, end-tidal CO2 and arterial pressure were recorded. Rp-cAMPS in the preBötzinger complex (preBötC) caused powerful, dose-dependent depression of phrenic burst amplitude and inspiratory period. Rp-cAMPS powerfully depressed burst amplitude in the phrenic premotor nucleus, but had no effect at the phrenic motor nucleus, suggesting a lack of persistent PKA activity here. Surprisingly, inhibition of PKA activity in the preBötC increased phrenic burst frequency, whereas in the Bötzinger complex phrenic frequency decreased. Pretreating the preBötC with strychnine, but not bicuculline, blocked the Rp-cAMPS-evoked increase in frequency, but not the depression of phrenic burst amplitude. We conclude that endogenous PKA activity in excitatory inspiratory preBötzinger neurons and phrenic premotor neurons, but not motor neurons, regulates network inspiratory drive currents that underpin the intensity of phrenic nerve discharge. We show that inhibition of PKA activity reduces tonic glycinergic transmission that normally restrains the frequency of rhythmic respiratory activity. Finally, we suggest that the maintenance of the respiratory rhythm in vivo is not dependent on endogenous cAMP-PKA signalling.
  European Journal of Neuroscience 04/2013;
• Article: Reward sensitivity modulates connectivity among reward brain areas during processing of anticipatory reward cues.

  Victor Costumero, Alfonso Barrós-Loscertales, Juan C Bustamante, Noelia Ventura-Campos, Paola Fuentes, César Avila
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  ABSTRACT: Reward sensitivity, or the tendency to engage in motivated approach behavior in the presence of rewarding stimuli, may be a contributory factor for vulnerability to disinhibitory behaviors. Although evidence exists for a reward sensitivity-related increased response in reward brain areas (i.e. nucleus accumbens or midbrain) during the processing of reward cues, it is unknown how this trait modulates brain connectivity, specifically the crucial coupling between the nucleus accumbens, the midbrain, and other reward-related brain areas, including the medial orbitofrontal cortex and the amygdala. Here, we analysed the relationship between effective connectivity and personality in response to anticipatory reward cues. Forty-four males performed an adaptation of the Monetary Incentive Delay Task and completed the Sensitivity to Reward scale. The results showed the modulation of reward sensitivity on both activity and functional connectivity (psychophysiological interaction) during the processing of incentive cues. Sensitivity to reward scores related to stronger activation in the nucleus accumbens and midbrain during the processing of reward cues. Psychophysiological interaction analyses revealed that midbrain-medial orbitofrontal cortex connectivity was negatively correlated with sensitivity to reward scores for high as compared with low incentive cues. Also, nucleus accumbens-amygdala connectivity correlated negatively with sensitivity to reward scores during reward anticipation. Our results suggest that high reward sensitivity-related activation in reward brain areas may result from associated modulatory effects of other brain regions within the reward circuitry.
  European Journal of Neuroscience 04/2013;
• Article: Diurnal rhythms in neural activation in the mesolimbic reward system: critical role of the medial prefrontal cortex.

  Ricardo M Baltazar, Lique M Coolen, Ian C Webb
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  ABSTRACT: Previous evidence suggests a circadian modulation of drug-seeking behavior and responsiveness to drugs of abuse. To identify potential mechanisms for rhythmicity in reward, a marker of neural activation (cFos) was examined across the day in the mesolimbic reward system. Rats were perfused at six times during the day [zeitgeber times (ZTs): 2, 6, 10, 14, 18, and 22], and brains were analysed for cFos and tyrosine hydroxylase (TH)-immunoreactive (IR) cells. Rhythmic expression of cFos was observed in the nucleus accumbens (NAc) core and shell, in the medial prefrontal cortex (mPFC), and in TH-IR and non-TH-IR cells in the ventral tegmental area (VTA), with peak expression during the late night and nadirs during the late day. No significant rhythmicity was observed in the basolateral amgydala or the dentate gyrus. As the mPFC provides excitatory input to both the NAc and VTA, this region was hypothesised to be a key mediator of rhythmic neural activation in the mesolimbic system. Hence, the effects of excitotoxic mPFC lesions on diurnal rhythms in cFos immunoreactivity at previously observed peak (ZT18) and nadir (ZT10) times were examined in the NAc and VTA. mPFC lesions encompassing the prelimbic and infralimbic subregions attenuated peak cFos immunoreactivity in the NAc, eliminating the diurnal rhythm, but had no effect on VTA rhythms. These results suggest that rhythmic neural activation in the mesolimbic system may contribute to diurnal rhythms in reward-related behaviors, and indicate that the mPFC plays a critical role in mediating rhythmic neural activation in the NAc.
  European Journal of Neuroscience 04/2013;
• Article: Adenosine A1 and A2A receptor-mediated modulation of acetylcholine release in the mice neuromuscular junction.

  Neus Garcia, Mercedes Priego, Teresa Obis, Manel M Santafe, Marta Tomàs, Nuria Besalduch, M Angel Lanuza, Josep Tomàs
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  ABSTRACT: Immunocytochemistry shows that purinergic receptors (P1Rs) type A1 and A2A (A1 R and A2 A R, respectively) are present in the nerve endings at the P6 and P30 Levator auris longus (LAL) mouse neuromuscular junctions (NMJs). As described elsewhere, 25 μm adenosine reduces (50%) acetylcholine release in high Mg(2+) or d-tubocurarine paralysed muscle. We hypothesize that in more preserved neurotransmission machinery conditions (blocking the voltage-dependent sodium channel of the muscle cells with μ-conotoxin GIIIB) the physiological role of the P1Rs in the NMJ must be better observed. We found that the presence of a non-selective P1R agonist (adenosine) or antagonist (8-SPT) or selective modulators of A1 R or A2 A R subtypes (CCPA and DPCPX, or CGS-21680 and SCH-58261, respectively) does not result in any changes in the evoked release. However, P1Rs seem to be involved in spontaneous release (miniature endplate potentials MEPPs) because MEPP frequency is increased by non-selective block but decreased by non-selective stimulation, with A1 Rs playing the main role. We assayed the role of P1Rs in presynaptic short-term plasticity during imposed synaptic activity (40 Hz for 2 min of supramaximal stimuli). Depression is reduced by micromolar adenosine but increased by blocking P1Rs with 8-SPT. Synaptic depression is not affected by the presence of selective A1 R and A2 A R modulators, which suggests that both receptors need to collaborate. Thus, A1 R and A2 A R might have no real effect on neuromuscular transmission in resting conditions. However, these receptors can conserve resources by limiting spontaneous quantal leak of acetylcholine and may protect synaptic function by reducing the magnitude of depression during repetitive activity.
  European Journal of Neuroscience 04/2013;
• Article: Social reward: interactions with social status, social communication, aggression, and associated neural activation in the ventral tegmental area.

  Mario Gil, Ngoc-Thao Nguyen, Mark McDonald, H Elliott Albers
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  ABSTRACT: Nearly all species engage in a variety of intraspecific social interactions, and there is evidence that these interactions are rewarding. Less is known, however, about the factors that influence social reward. Using the conditioned place preference paradigm, we tested whether social interactions are rewarding for male Syrian hamsters. We also tested whether social stimuli increase neural activation in the ventral tegmental area (VTA), a component of the mesolimbic reward system, and how individual differences in social behavior and experience influence neural activation. In the present study, we found that hamsters developed a conditioned place preference for social interactions, but the effects were significantly stronger in dominant animals compared with subordinates. The number of Fos-immunoreactive cells in the VTA was significantly higher in hamsters that had engaged in a direct social encounter compared with hamsters exposed to a caged stimulus hamster or controls. Interestingly, socially experienced males had more Fos-immunoreactive cells in the VTA than socially naive males after exposure to a social stimulus. Surprisingly, the amount of Fos immunoreactivity in the VTA induced by a social stimulus was correlated with the amount of aggressive/dominance behaviors that had been observed during interactions that had occurred 2 months earlier. Our results indicate that social interactions between males are rewarding, and that social dominance increases the reward value. Social interactions stimulate the mesolimbic reward system, and social experience enhances its response to novel social stimuli and may produce long-term changes in the neural mechanisms that mediate the maintenance of dominance over long periods of time.
  European Journal of Neuroscience 04/2013;
• Article: Syntenin-a promotes spinal cord regeneration following injury in adult zebrafish.

  Yong Yu, Melitta Schachner
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  ABSTRACT: In contrast to mammals, adult zebrafish recover locomotor function after spinal cord injury, in part due to the capacity of the central nervous system to repair severed connections. To identify molecular cues that underlie regeneration, we conducted mRNA expression profiling and found that syntenin-a expression is upregulated in the adult zebrafish spinal cord caudal to the lesion site after injury. Syntenin is a scaffolding protein involved in mammalian cell adhesion and movement, axonal outgrowth, establishment of cell polarity, and protein trafficking. It could thus be expected to be involved in supporting regeneration in fish. Syntenin-a mRNA and protein are expressed in neurons, glia and newly generated neural cells, and upregulated caudal to the lesion site on days 6 and 11 following spinal cord injury. Treatment of spinal cord-injured fish with two different antisense morpholinos to knock down syntenin-a expression resulted in significant inhibition of locomotor recovery at 5 and 6 weeks after injury, when compared to control morpholino-treated fish. Knock-down of syntenin-a reduced regrowth of descending axons from brainstem neurons into the spinal cord caudal to the lesion site. These observations indicate that syntenin-a is involved in regeneration after traumatic insult to the central nervous system of adult zebrafish, potentially leading to novel insights into the cellular and molecular mechanisms that require activation in the regeneration-deficient mammalian central nervous system.
  European Journal of Neuroscience 04/2013;
• Article: Neuronal differentiation requires a biphasic modulation of gap junctional intercellular communication caused by dynamic changes of connexin43 expression.

  Heiko Lemcke, Marie-Louise Nittel, Dieter G Weiss, Sergei A Kuznetsov
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  ABSTRACT: It was suggested that gap junctional intercellular communication (GJIC) and connexin (Cx) proteins play a crucial role in cell proliferation and differentiation. However, the mechanisms of cell coupling in regulating cell fate during embryonic development are poorly understood. To study the role of GJIC in proliferation and differentiation, we used a human neural progenitor cell line derived from the ventral mesencephalon. Fluorescence recovery after photobleaching (FRAP) showed that dye coupling was extensive in proliferating cells but diminished after the induction of differentiation, as indicated by a 2.5-fold increase of the half-time of fluorescence recovery. Notably, recovery half-time decreased strongly (five-fold) in the later stage of differentiation. Western blot analysis revealed a similar time-dependent expression profile of Cx43, acting as the main gap junction-forming protein. Interestingly, large amounts of cytoplasmic Cx43 were retained mainly in the Golgi network during proliferation but decreased when differentiation was induced. Furthermore, down-regulation of Cx43 by small interfering RNA reduced functional cell coupling, which in turn resulted in a 50% decrease of both the proliferation rate and neuronal differentiation. Our findings suggest a dual function of Cx43 and GJIC in the neural development of ReNcell VM197 human progenitor cells. GJIC accompanied by high Cx43 expression is necessary (1) to maintain cells in a proliferative state and (2) to complete neuronal differentiation, including the establishment of a neural network. However, uncoupling of cells is crucial in the early stage of differentiation during cell fate commitment.
  European Journal of Neuroscience 04/2013;
• Article: BOLD human responses to chromatic spatial features.

  E Castaldi, F Frijia, D Montanaro, M Tosetti, M C Morrone
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  ABSTRACT: Animal physiological and human psychophysical studies suggest that an early step in visual processing involves the detection and identification of features such as lines and edges, by neural mechanisms with even- and odd-symmetric receptive fields. Functional imaging studies also demonstrate mechanisms with even- and odd-receptive fields in early visual areas, in response to luminance-modulated stimuli. In this study we measured fMRI BOLD responses to 2-D stimuli composed of only even or only odd symmetric features, and to an amplitude-matched random noise control, modulated in red-green equiluminant colour contrast. All these stimuli had identical power but different phase spectra, either highly congruent (even or odd symmetry stimuli) or random (noise). At equiluminance, V1 BOLD activity showed no preference between congruent- and random-phase stimuli, as well as no preference between even and odd symmetric stimuli. Areas higher in the visual hierarchy, both along the dorsal pathway (caudal part of the intraparietal sulcus, dorsal LO and V3A) and the ventral pathway (V4), responded preferentially to odd symmetry over even symmetry stimuli, and to congruent over random phase stimuli. Interestingly, V1 showed an equal increase in BOLD activity at each alternation between stimuli of different symmetry, suggesting the existence of specialised mechanisms for the detection of edges and lines such as even- and odd-chromatic receptive fields. Overall the results indicate a high selectivity of colour-selective neurons to spatial phase along both the dorsal and the ventral pathways in humans.
  European Journal of Neuroscience 04/2013;
• Article: Striatal modulation of BDNF expression using microRNA124a-expressing lentiviral vectors impairs ethanol-induced conditioned-place preference and voluntary alcohol consumption.

  Amine Bahi, Jean-Luc Dreyer
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  ABSTRACT: Alcohol abuse is a major health, economic and social concern in modern societies, but the exact molecular mechanisms underlying ethanol addiction remain elusive. Recent findings show that small non-coding microRNA (miRNA) signaling contributes to complex behavioral disorders including drug addiction. However, the role of miRNAs in ethanol-induced conditioned-place preference (CPP) and voluntary alcohol consumption has not yet been directly addressed. Here, we assessed the expression profile of miR124a in the dorsal striatum of rats upon ethanol intake. The results show that miR124a was downregulated in the dorso-lateral striatum (DLS) following alcohol drinking. Then, we identified brain-derived neurotrophic factor (BDNF) as a direct target of miR124a. In fact, BDNF mRNA was upregulated following ethanol drinking. We used lentiviral vector (LV) gene transfer technology to further address the role of miR124a and its direct target BDNF in ethanol-induced CPP and alcohol consumption. Results reveal that stereotaxic injection of LV-miR124a in the DLS enhances ethanol-induced CPP as well as voluntary alcohol consumption in a two-bottle choice drinking paradigm. Moreover, miR124a-silencer (LV-siR124a) as well as LV-BDNF infusion in the DLS attenuates ethanol-induced CPP as well as voluntary alcohol consumption. Importantly, LV-miR124a, LV-siR124a and LV-BDNF have no effect on saccharin and quinine intake. Our findings indicate that striatal miR124a and BDNF signaling have crucial roles in alcohol consumption and ethanol conditioned reward.
  European Journal of Neuroscience 04/2013;