Abnormal Functional Organization in the Dorsal Lateral Geniculate Nucleus of Mice Lacking the β2 Subunit of the Nicotinic Acetylcholine Receptor (original) (raw)

2003, Neuron

https://doi.org/10.1016/S0896-6273(03)00789-X

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Abstract

activity. Between postnatal day 1 (P1) and P10 in this species, spontaneous activity is mediated by nicotinic cholinergic transmission (Feller et al., 1996; Penn et al., 1998) and, in the form of either action potential firing (Meister et al., 1991) or transient influxes of calcium (e.g.,

Immunohistochemical localization of a neuronal nicotinic acetylcholine receptor in mammalian brain

Proceedings of the National Academy of Sciences, 1987

A monoclonal antibody generated against purified acetylcholine receptor from Torpedo electric organ was used to immunohistochemically localize a neuronal nicotinic acetylcholine receptor. Regions of the rat brain stained with this antibody paralleled those areas of the brain exhibiting [3H]nicotine binding sites and corresponded to areas in which mRNAs encoding for alpha subunits of the neuronal nicotinic acetylcholine receptor are present. Thus, the anteroventral thalamus, cortex, hippocampus, medial habenula, interpeduncular nucleus, and substantia nigra/ventral tegmental area exhibited significant immunoreactivity. Neurons of the medial habenula and substantia nigra were densely stained, and processes were prominently delineated. Furthermore, in the projection areas of the medial habenula (interpeduncular nucleus and median raphe) axons were strongly immunoreactive and were distributed to distinct subdivisions of the target sites. The present data suggest that there are several d...

Distribution of nicotinic acetylcholine receptor subunits α7 and β2 in the human brainstem and hippocampal formation

Journal of Chemical Neuroanatomy, 2010

We provide the first quantification and localization of the nicotinic acetylcholine receptors (nAChRs) a7 and b2 in the human adult and infant brainstem and hippocampus. After applying immunohistochemistry on formalin fixed and paraffin embedded human brain tissue, we qualitatively analyzed the staining to provide a comparison in expression amongst the brainstem nuclei and hippocampal regions, and between the infants and adults. Amongst the brainstem regions studied, the greatest protein expression for both a7 and b2 subunits was in the motor nuclei of the medulla and pons. Lowest expression for both subunits was in the midbrain nuclei, except for the oculomotor nucleus. Comparison between infants and adults showed greater expression in the infant brainstem nuclei of the dorsal motor nucleus of the vagus, hypoglossal, inferior olivary nucleus, nucleus of the solitary tract, abducens, and facial nuclei, for both a7 and b2 nAChRs. In the hippocampus, only the a7 subunit showed greater expression in infants compared to adults. We conclude that both a7 and b2 containing nAChRs play an important role in many nuclei of the human infant and adult brainstem, and that the a7 subunit may have a more prominent role in the infant than adult hippocampus. ß

Stable expression in HEK-293 cells of the rat α3/β4 subtype of neuronal nicotinic acetylcholine receptor

FEBS letters, 1996

The tz31]~4 subtype of neuronal nicotinic acetylcholine receptor (nAChR) was stably expressed in human embryonic kidney (HEK) 293 cells that co-expressed a voltage-gated Ca 2+ channel. ¢z3/134-nAChR-expressing clones were identified using the fura-2 Ca 2÷ imaging technique, and were further characterised by single-cell and whole-cell patch-clamp studies. Acetylcholine (ACh) induced fast activating currents which showed desensitisation and inward rectification. The conductance of the ACh-activated channel was 29 pS. The order of potency of the nicotinic agonists tested was cytisine -=-nicotine > acetylcholine. The ECs0 value for ACh was 145 I~VI; the Hill coefficient was close to 2. The currents elicited by ACh were effectively blocked by nicotinic antagonists, but not by the muscarinic antagonist atropine. These properties are comparable to the pharmacological and physiological profile of ganglionic nicotinic receptors and type III currents of cultured Idppocampal neurons.

Co-expression of α7 and β2 nicotinic acetylcholine receptor subunit mRNAs within rat brain cholinergic neurons

Neuroscience, 2003

Nicotine enhances cognitive and attentional processes through stimulation of the basal forebrain cholinergic system. Although muscarinic cholinergic autoreceptors have been well characterized, pharmacological characterization of nicotinic autoreceptors has proven more difficult. The present study used double-labeling in situ hybridization to determine expression of nicotinic acetylcholine receptor (nAChR) subunit mRNAs within basal forebrain cholinergic neurons in order to gain information about possible nAChR autoreceptor properties. Cholinergic cells of the mesopontine tegmentum and striatal interneurons were also examined, as were septohippocampal GABAergic neurons that interact with cholinergic neurons to regulate hippocampal activity. ␣7 and ␤2 nAChR mRNAs were found to be coexpressed in almost all cholinergic cells and in the majority of GABAergic neurons examined. ␣4 nAChR mRNA expression was restricted to cholinergic cells of the nucleus basalis magnocellularis, and to non-cholinergic cells of the medial septum and mesopontine tegmentum.

Developmental Excitation of Corticothalamic Neurons by Nicotinic Acetylcholine Receptors

Journal of Neuroscience, 2008

In this study, we show robust nicotinic excitation of pyramidal neurons in layer VI of prefrontal cortex. This layer contains the corticothalamic neurons, which gate thalamic activity and play a critical role in attention. Our experiments tested nicotinic excitation across postnatal development, using whole-cell recordings in prefrontal brain slices from rats. These experiments showed that layer VI neurons have peak nicotinic currents during the first postnatal month, a time period of intensive cortical development in rodents. We demonstrate that these currents are mediated directly by postsynaptic nicotinic receptors and can be suppressed by a competitive antagonist of alpha(4)beta(2)* nicotinic receptors. To record from identified corticothalamic neurons, we performed stereotaxic surgery to label the neurons projecting to medial dorsal thalamus. As hypothesized, recordings from these retrogradely labeled neurons in layer VI showed prominent nicotinic currents. Finally, we examined the effects of the drug nicotine on layer VI neurons and probed for the potential involvement of the accessory subunit, alpha(5), in their receptors. A level of nicotine similar to that found in the blood of smokers elicits a stable inward current in layer VI neurons, yet this exposure desensitizes approximately 50% of the subsequent current elicited by acetylcholine. An allosteric modulator of alpha(4)beta(2)alpha(5) receptors resulted in a 2.5-fold potentiation of submaximal nicotinic currents. This result is consistent with the expression of the relatively rare alpha(5) nicotinic subunit in layer VI. In summary, we show that layer VI corticothalamic neurons can be strongly excited during development by an unusual subtype of nicotinic receptor.

Nicotinic receptor subtype-selective circuit patterns in the subthalamic nucleus

The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015

The glutamatergic subthalamic nucleus (STN) exerts control over motor output through nuclei of the basal ganglia. High-frequency electrical stimuli in the STN effectively alleviate motor symptoms in movement disorders, and cholinergic stimulation boosts this effect. To gain knowledge about the mechanisms of cholinergic modulation in the STN, we studied cellular and circuit aspects of nicotinic acetylcholine receptors (nAChRs) in mouse STN. We discovered two largely divergent microcircuits in the STN; these are regulated in part by either α4β2 or α7 nAChRs. STN neurons containing α4β2 nAChRs (α4β2 neurons) received more glutamatergic inputs, and preferentially innervated GABAergic neurons in the substantia nigra pars reticulata. In contrast, STN neurons containing α7 nAChRs (α7 neurons) received more GABAergic inputs, and preferentially innervated dopaminergic neurons in the substantia nigra pars compacta. Interestingly, local electrical stimuli excited a majority (79%) of α4β2 neuro...

Neurotransmitter regulation of neural development: acetylcholine and nicotinic receptors

Anais da Academia Brasileira de Ciências, 2002

Several neurotransmitter systems have been related to developmental processes during the past decade. In this review, we discuss the evidence that the nicotinic acetylcholine receptors could have an additional function during development that may be unrelated to their role in cholinergic neurotransmission in the vertebrate brain. Both temporal expression data and in vitro and in vivo studies with nicotinic agonists and antagonists have provided direct support for a role of nicotinic receptors in neural developmental processes such as neurite outgrowth and differentiation. A similar picture has emerged for other neurotransmitter and receptor systems as well, which generates a new view of neural processes during both development and mature life.

Synaptic transmission at nicotinic acetylcholine receptors in rat hippocampal organotypic cultures and slices

The Journal of Physiology, 1999

Despite its predominant role in the peripheral nervous system and particularly at the motor endplate where it was first discovered, fast nicotinic cholinergic transmission has been found up to now only exceptionally in the central nervous system. One classic example is the synaptic activation of the Renshaw cell in the spinal cord, which receives a cholinergic nicotinic input from motoneurones (Eccles et al. 1954). Similarly, synaptic nicotinic potentials have been reported in brainstem vagal motoneurones (Zhang et al. 1993) and neuronal nicotinic acetylcholine receptor (nAChR) mediated responses could at least in part mediate dopamine release in the striatum (Clarke et al. 1987; Futami et al. 1995). So far, however, there has been no report of fast cholinergic transmission in mammalian cortical regions. Contrasting with this, nicotine has been shown to play a major role in modulating brain functions (Wonnacott, 1997). Recent developments in gene technology have revealed the presence in many brain areas of mRNA coding for different nicotinic receptor subtypes (Goldman et al. 1987; Sargent, 1993). Furthermore, the presence of these mRNAs correlates well with reports of the existence of specific binding sites for both ACh analogues and the selective nicotinic receptor antagonist á_bungarotoxin (á-BgTX; Clarke et al. 1985). In addition, electrophysiological studies made on dissociated hippocampal neurones have demonstrated the existence of functional nicotinic receptors and identified several types of nicotinic currents (Alkondon & Albuquerque, 1993; Albuquerque et al. 1997). Finally, strong evidence implicates nicotinic acetylcholine receptors in behaviour, learning and memory as well as in the reinforcing actions of nicotine (Role & Berg, 1996; Picciotto et al. 1998). A major issue, therefore, has been to understand whether neuronal nAChRs have purely a modulatory role, representing mainly targets for the low concentrations of nicotine that reach the brain during smoking, or whether, as found in the peripheral nervous system, they also mediate fast synaptic transmission. This is not unlikely considering the evidence showing the existence in the hippocampus of a

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Functional Nicotinic Acetylcholine Receptor Expression on Stem and Progenitor Cells of the Early Embryonic Nervous System

Annals of the New York Academy of Sciences, 2002

dependent induction and expression of functional plasticity in the barrel cortex of the adult rat. J Neurophysiol 86: 422-437, 2001. Feller MB. The role of nAChR-mediated spontaneous retinal activity in visual system development. J Neurobiol 53: 556-567, 2002. Flores CM, Rogers SW, Pabreza LA, Wolfe BB and Kellar KJ. A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment. Mol Pharmacol 41: 31-37, 1992.

Postnatal development of two nicotinic cholinergic receptors in seven mouse brain regions

International Journal of Developmental Neuroscience, 1990

The developmental profiles for binding of ~-['~I]b~garotoxin and L-[3H]nicotine to putative nicotinic cholinergic receptors were determined in seven mouse brain regions. The overall pattern of development of a-bungarotoxin binding was similar in all of the regions. Neonatal binding values tended to be greater than those observed in adult brain regions. Maximal binding occurred within 10 days of birth and adult binding values were reached by 20 days of age. The patterns of development of nicotine binding in each of the seven brain regions differed according to re8ion. Gross similarities in developmental protiles for nicotine binding were found among the more caudal and among the more rostra1 regions. In hindbr~n and cerebellum, maxima1 nicotine binding was found at birth (5 days of age in cerebellum); binding declined approximately 4-fold by 20 days and remained relatively constant thereafter. In midbrain and hypothalamus, a less extensive decrease in nicotine binding occurred from birth to adulthood (midbrain, 25%; hypothalamus, 50%). Nicotine binding in hippocampus and cortex remained unchanged between birth and adulthood. The developmental pattern for nicotine binding in striatum differed from that found in the other brain repions. At 5 days of age, binding was about 65% of adult binding, which was reached at 30 days of age. In most of the brain regions the developmental profile for n-bungarotoxin binding was different from that of nicotine. This difference. was especially notable in striatum, where adult nicotine binding was higher than neonatal nicotine binding, whereas adult a-bungarotoxin binding was lower than neonatal a-bungarotoxin binding.

Nicotinic Acetylcholine Receptors and Nicotinic Cholinergic Mechanisms of the Central Nervous System

Annual Review of Pharmacology and Toxicology, 2007

Subtypes of neuronal nicotinic acetylcholine receptors (nAChRs) are constructed from numerous subunit combinations that compose channel-receptor complexes with varied functional and pharmacological characteristics. Structural and functional diversity and the broad presynaptic, postsynaptic, and nonsynaptic locations of nAChRs underlie their mainly modulatory roles throughout the mammalian brain. Presynaptic and preterminal nicotinic receptors enhance neurotransmitter release, postsynaptic nAChRs contribute a small minority of fast excitatory transmission, and nonsynaptic nAChRs modulate many neurotransmitter systems by influencing neuronal excitability. Nicotinic receptors have roles in development and synaptic plasticity, and nicotinic mechanisms participate in learning, memory, and attention. Decline, disruption, or alterations of nicotinic cholinergic mechanisms contribute to dysfunctions such as epilepsy, schizophrenia, Parkinson's disease, autism, dementia with Lewy bodies,...

Neuronal nicotinic acetylcholine receptor subunit knockout mice: physiological and behavioral phenotypes and possible clinical implications

Pharmacology & Therapeutics, 2001

Nicotinic acetylcholine receptors (nAChRs) in the muscle, autonomic ganglia, and brain are targets for pharmacologically administered nicotine. Several of the subunits that combine to form neuronal nicotinic receptors have been deleted by knockout or mutated by knockin in mice using homologous recombination. We will review the biochemical, pharmacological, anatomical, physiological, and behavioral phenotypes of mice with genetically altered neuronal nAChR subunits. Clinically relevant mutations in nAChR genes will also be discussed. In addition, some of the signal transduction pathways activated through nAChRs will be described in order to delineate the longer-term changes that might result from persistent activation or inactivation of nAChRs. Genetically manipulated mice have greatly increased our understanding of the subunit composition and physiological properties of nAChRs in vivo. In addition, these mice have provided a model system to determine the molecular basis for many of the pharmacological actions of nicotine on neurotransmitter release and behavior. Genetic manipulations in mice have also elucidated the role of nAChR subunits in various disease states, and suggest several avenues for drug development. D

Function of Mammalian Nicotinic Acetylcholine Receptors

Nicotinic Acetylcholine Receptor, 1986

This paper will briefly review the results of our studies of the function of the nicotinic acetylcholine receptors (AChRs) expressed by clonal mammalian BC3H-1 cells in vitro. The observations and interpretations will be compared with expectations based on the physiology of junctional transmission and with data obtained by others. BC3H-1 cells are a cell line which originated in a brain tumor of C3H mice (Schubert et al., 1974). These cells differentiate in culture and express a large number of AChR. A number of studies have established that the AChR are similar to skeletal muscle receptors biochemically (Boulter and Patrick, 1977), pharmacologically (Patrick et al., 1977; Sine and Taylor, 1981) and in the primary amino acid sequence of the subunits (LaPolla et al., 1984; Boulter et aI, 1985). The methods used have been described (Sine and Steinbach, 1984a,b; 1986a,b,c). The data discussed here were obtained at 11°C using cell attached patches. Cells

Developmental regulation of nicotinic acetylcholine receptors within midbrain dopamine neurons

Neuroscience, 2007

We have combined anatomical and functional methodologies to provide a comprehensive analysis of the properties of nicotinic acetylcholine receptors (nAChRs) on developing dopamine (DA) neurons. Double-labeling in situ hybridization was used to examine the expression of nAChR subunit mRNAs within developing midbrain DA neurons. As brain maturation progressed there was a change in the pattern of subunit mRNA expression within DA neurons, such that α3 and α4 subunits declined and α6 mRNA increased. Although there were strong similarities in subunit mRNA expression in substantia nigra (SNc) and ventral tegmental area (VTA), there was higher expression of α4 mRNA in SNc than VTA at gestational day (G)15, and of α5, α6 and β3 mRNAs during postnatal development. Using a superfusion neurotransmitter release paradigm to functionally characterize nicotine-stimulated release of [ 3 H]DA from striatal slices, the properties of the nAChRs on DA terminals were also found to change with age. Functional nAChRs were detected on striatal terminals at G18. There was a decrease in maximal release in the first postnatal week, followed by an increase in nicotine efficacy and potency during the second and third postnatal weeks. In the transition from adolescence (postnatal days (P) 30 and 40) to adulthood, there was a complex pattern of functional maturation of nAChRs in ventral, but not dorsal, striatum. In males, but not females, there were significant changes in both nicotine potency and efficacy during this developmental period. These findings suggest that nAChRs may play critical functional roles throughout DA neuronal maturation.

Neural Systems Governed by Nicotinic Acetylcholine Receptors: Emerging Hypotheses

Neuron, 2011

Cholinergic neurons and nicotinic acetylcholine receptors (nAChRs) in the brain participate in diverse functions: reward, learning and memory, mood, sensory processing, pain, and neuroprotection. Nicotinic systems also have well-known roles in drug abuse. Here, we review recent insights into nicotinic function, linking exogenous and endogenous manipulations of nAChRs to alterations in synapses, circuits, and behavior. We also discuss how these contemporary advances can motivate attempts to exploit nicotinic systems therapeutically in Parkinson's disease, cognitive decline, epilepsy, and schizophrenia.

Early development of two types of nicotinic acetylcholine receptors

The Journal of neuroscience : the official journal of the Society for Neuroscience, 1988

Functional changes of acetylcholine receptor (AChR) channels in embryonic Xenopus myotomal muscle cells were examined during their development in culture. Single-channel currents evoked by 50 or 500 nM ACh were measured using the patch-clamp technique. In Xenopus myocytes the first emergence of AChRs takes place at about stage 20 (Nieuwkoop and Faber). Myotomes were dissociated at very early stages and plated in culture. Single-channel currents through AChRs were recorded at times ranging from a few hours (stage 21) to several days (stage 47) after the first emergence of AChRs. Two classes of AChR channel were recorded: One class had a low conductance with a long burst duration (low-conductance channel), and the other had a high conductance with a short burst duration (high-conductance channel). Both of these classes were active from the earliest time recorded (stages 21-24). One effect of development was a shift in the relative activity of the low- and high-conductance channels. In...

Functional Nicotinic Acetylcholine Receptors Are Expressed in B Lymphocyte-Derived Cell Lines

Molecular Pharmacology, 2003

dependent induction and expression of functional plasticity in the barrel cortex of the adult rat. J Neurophysiol 86: 422-437, 2001. Feller MB. The role of nAChR-mediated spontaneous retinal activity in visual system development. J Neurobiol 53: 556-567, 2002. Flores CM, Rogers SW, Pabreza LA, Wolfe BB and Kellar KJ. A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment. Mol Pharmacol 41: 31-37, 1992.

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Role of adenylate cyclase 1 in retinofugal map development

The Journal of Comparative Neurology, 2012

The development of topographic maps of the sensory periphery is sensitive to the disruption of adenylate cyclase 1 (AC1) signaling. AC1 catalyzes the production of cAMP in a Ca 2þ /calmodulin-dependent manner, and AC1 mutant mice (AC1 À/À ) have disordered visual and somatotopic maps. However, the broad expression of AC1 in the brain and the promiscuous nature of cAMP signaling have frustrated attempts to determine the underlying mechanism of AC1-dependent map development. In the mammalian visual system, the initial coarse targeting of retinal ganglion cell (RGC) projections to the superior colliculus (SC) and lateral geniculate nucleus (LGN) is guided by molecular cues, and the subsequent refinement of these crude projections occurs via an activity-dependent process that depends on spontaneous retinal waves. Here, we show that O.S. Dhande's current address is

Modeling Activity and Target-Dependent Developmental Cell Death of Mouse Retinal Ganglion Cells Ex Vivo

Plos One, 2012

Programmed cell death is widespread during the development of the central nervous system and serves multiple purposes including the establishment of neural connections. In the mouse retina a substantial reduction of retinal ganglion cells (RGCs) occurs during the first postnatal week, coinciding with the formation of retinotopic maps in the superior colliculus (SC). We previously established a retino-collicular culture preparation which recapitulates the progressive topographic ordering of RGC projections during early post-natal life. Here, we questioned whether this model could also be suitable to examine the mechanisms underlying developmental cell death of RGCs. Brn3a was used as a marker of the RGCs. A developmental decline in the number of Brn3a-immunolabelled neurons was found in the retinal explant with a timing that paralleled that observed in vivo. In contrast, the density of photoreceptors or of starburst amacrine cells increased, mimicking the evolution of these cell populations in vivo. Blockade of neural activity with tetrodotoxin increased the number of surviving Brn3a-labelled neurons in the retinal explant, as did the increase in target availability when one retinal explant was confronted with 2 or 4 collicular slices. Thus, this ex vivo model reproduces the developmental reduction of RGCs and recapitulates its regulation by neural activity and target availability. It therefore offers a simple way to analyze developmental cell death in this classic system. Using this model, we show that ephrin-A signaling does not participate to the regulation of the Brn3a population size in the retina, indicating that eprhin-A-mediated elimination of exuberant projections does not involve developmental cell death.

Ephrin-As and neural activity are required for eye-specific patterning during retinogeniculate mapping

Nature Neuroscience, 2005

In mammals, retinal ganglion cell (RGC) projections initially intermingle and then segregate into a stereotyped pattern of eyespecific layers in the dorsal lateral geniculate nucleus (dLGN). Here we found that in mice deficient for ephrin-A2, ephrin-A3 and ephrin-A5, eye-specific inputs segregated but the shape and location of eye-specific layers were profoundly disrupted. In contrast, mice that lacked correlated retinal activity did not segregate eye-specific inputs. Inhibition of correlated neural activity in ephrin mutants led to overlapping retinal projections that were located in inappropriate regions of the dLGN. Thus, ephrin-As and neural activity act together to control patterning of eye-specific retinogeniculate layers.

Deletion of Ten-m3 Induces the Formation of Eye Dominance Domains in Mouse Visual Cortex

Cerebral Cortex, 2013

The visual system is characterized by precise retinotopic mapping of each eye, together with exquisitely matched binocular projections. In many species, the inputs that represent the eyes are segregated into ocular dominance columns in primary visual cortex (V1), whereas in rodents, this does not occur. Ten-m3, a member of the Ten-m/Odz/Teneurin family, regulates axonal guidance in the retinogeniculate pathway. Significantly, ipsilateral projections are expanded in the dorsal lateral geniculate nucleus and are not aligned with contralateral projections in Ten-m3 knockout (KO) mice. Here, we demonstrate the impact of altered retinogeniculate mapping on the organization and function of V1. Transneuronal tracing and c-fos immunohistochemistry demonstrate that the subcortical expansion of ipsilateral input is conveyed to V1 in Ten-m3 KOs: Ipsilateral inputs are widely distributed across V1 and are interdigitated with contralateral inputs into eye dominance domains. Segregation is confirmed by optical imaging of intrinsic signals. Single-unit recording shows ipsilateral, and contralateral inputs are mismatched at the level of single V1 neurons, and binocular stimulation leads to functional suppression of these cells. These findings indicate that the medial expansion of the binocular zone together with an interocular mismatch is sufficient to induce novel structural features, such as eye dominance domains in rodent visual cortex.

Modeling Development in Retinal Afferents: Retinotopy, Segregation, and EphrinA/EphA Mutants

PLoS ONE, 2014

During neural development, neurons extend axons to target areas of the brain. Through processes of growth, branching and retraction these axons establish stereotypic patterns of connectivity. In the visual system, these patterns include retinotopic organization and the segregation of individual axons onto different subsets of target neurons based on the eye of origin (ocular dominance) or receptive field type (ON or OFF). Characteristic disruptions to these patterns occur when neural activity or guidance molecule expression is perturbed. In this paper we present a model that explains how these developmental patterns might emerge as a result of the coordinated growth and retraction of individual axons and synapses responding to position-specific markers, trophic factors and spontaneous neural activity. This model derives from one presented earlier (Godfrey et al., 2009) but which is here extended to account for a wider range of phenomena than previously described. These include ocular dominance and ON-OFF segregation and the results of altered ephrinA and EphA guidance molecule expression. The model takes into account molecular guidance factors, realistic patterns of spontaneous retinal wave activity, trophic molecules, homeostatic mechanisms, axon branching and retraction rules and intra-axonal signaling mechanisms that contribute to the survival of nearby synapses on an axon. We show that, collectively, these mechanisms can account for a wider range of phenomena than previous models of retino-tectal development.

Lateral geniculate neurons projecting to primary visual cortex show ocular dominance plasticity in adult mice

Nature neuroscience, 2017

Experience-dependent plasticity in the mature visual system is widely considered to be cortical. Using chronic two-photon Ca imaging of thalamic afferents in layer 1 of binocular visual cortex, we provide evidence against this tenet: the respective dorsal lateral geniculate nucleus (dLGN) cells showed pronounced ocular dominance (OD) shifts after monocular deprivation in adult mice. Most (86%), but not all, of dLGN cell boutons were monocular during normal visual experience. Following deprivation, initially deprived-eye-dominated boutons reduced or lost their visual responsiveness to that eye and frequently became responsive to the non-deprived eye. This cannot be explained by eye-specific cortical changes propagating to dLGN via cortico-thalamic feedback because the shift in dLGN responses was largely resistant to cortical inactivation using the GABA receptor agonist muscimol. Our data suggest that OD shifts observed in the binocular visual cortex of adult mice may at least partial...

Fine-scale topography in sensory systems: insights from Drosophila and vertebrates

Journal of Comparative Physiology A, 2015

To encode the positions of sensory stimuli, sensory circuits form topographic maps in the central nervous system through specific point-to-point connections between pre-and post-synaptic neurons. In vertebrate visual systems, the establishment of topographic maps involves the formation of a coarse topography followed by that of fine-scale topography that distinguishes the axon terminals of neighboring neurons. It is known that intrinsic differences in the form of broad gradients of guidance molecules instruct coarse topography while neuronal activity is required for fine-scale topography. On the other hand, studies in the Drosophila visual system have shown that intrinsic differences in cell adhesion among the axon terminals of neighboring neurons instruct the fine-scale topography. Recent studies on activity-dependent topography in the Drosophila somatosensory system have revealed a role of neuronal activity in creating molecular differences among sensory neurons for establishing fine-scale topography, implicating a conserved principle. Here we review the findings in both Drosophila and vertebrates and propose an integrated model for fine-scale topography.

Manipulating the Level of Sensorimotor Stimulation during LI-rTMS Can Improve Visual Circuit Reorganisation in Adult Ephrin-A2A5-/- Mice

International Journal of Molecular Sciences, 2022

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has the potential to treat a variety of neurologic and psychiatric disorders. The extent of rTMS-induced neuroplasticity may be dependent on a subject's brain state at the time of stimulation. Chronic low intensity rTMS (LI-rTMS) has previously been shown to induce beneficial structural and functional reorganisation within the abnormal visual circuits of ephrin-A2A5 -/-mice in ambient lighting. Here, we administered chronic LI-rTMS in adult ephrin-A2A5 -/-mice either in a dark environment or concurrently with voluntary locomotion. One day after the last stimulation session, optokinetic responses were assessed and fluorescent tracers were injected to map corticotectal and geniculocortical projections. We found that LI-rTMS in either treatment condition refined the geniculocortical map. Corticotectal projections were improved in locomotion+LI-rTMS subjects, but not in dark + LI-rTMS and sham groups. Visuomotor behaviour was not improved in any condition. Our results suggest that the beneficial reorganisation of abnormal visual circuits by rTMS can be significantly influenced by simultaneous, ambient visual input and is enhanced by concomitant physical exercise. Furthermore, the observed pathway-specific effects suggest that regional molecular changes and/or the relative proximity of terminals to the induced electric fields influence the outcomes of LI-rTMS on abnormal circuitry.