Geniculate Neurons Research Articles

Impact of acute visual experience on development of LGN receptive fields in the ferret.

Selectivity for direction of motion is a key feature of primary visual cortical neurons. Visual experience is required for direction selectivity in carnivore and primate visual cortex, but the circuit mechanisms of its formation remain incompletely understood. Here we examined how developing lateral geniculate nucleus (LGN) neurons may contribute to cortical direction selectivity. Using in vivo electrophysiology techniques, we examined LGN receptive field properties of visually naïve female ferrets before and after exposure to 6 hours of motion stimuli in order to assess the effect of acute visual experience on LGN cell development. We found that acute experience with motion stimuli did not significantly affect the weak orientation or direction selectivity of LGN neurons. In addition, we found that neither latency nor sustainedness or transience of LGN neurons significantly changed with acute experience. These results suggest that the direction selectivity that emerges in cortex after acute experience is computed in cortex and cannot be explained by changes in LGN cells.SIGNIFICANCE STATEMENT:The development of typical neural circuitry requires experience-independent and experience-dependent factors. In the visual cortex of carnivores and primates, selectivity for motion arises as a result of experience, but we do not understand whether the major brain area that sits between the retina and the visual cortex - the lateral geniculate nucleus of the thalamus - also participates. Here we found that lateral geniculate neurons do not exhibit changes as a result of several hours of visual experience with moving stimuli, at a time when visual cortical neurons undergo a rapid change. We conclude that lateral geniculate neurons do not participate in this plasticity, and that changes in cortex are likely responsible for the development of direction selectivity in carnivores and primates.

Regional specialization of the tongue revealed by gustatory ganglion imaging.

Gustatory information is relayed from the anterior tongue by geniculate ganglion neurons and from the posterior tongue by neurons of the petrosal portion of the jugular/nodose/petrosal ganglion complex. Here, we use invivo calcium imaging in mice to compare the encoding of taste information in the geniculate and petrosal ganglia, at single-neuron resolution. Our data support an anterior/posterior specialization of taste information coding from the tongue to the ganglia, with petrosal neurons more responsive to umami or bitter and less responsive to sweet or salty stimuli than geniculate neurons. We found that umami (50mM MPG+ 1mM IMP) promotes salivation when applied to the posterior, but not anterior, tongue. This suggests a functional taste map of the mammalian tongue where the anterior and posterior taste pathways are differentially responsive to specific taste qualities, and differentially regulate downstream physiological functions of taste, such as promoting salivation.

Oral Sensory Neurons of the Geniculate Ganglion That Express Tyrosine Hydroxylase Comprise a Subpopulation That Contacts Type II and Type III Taste Bud Cells.

Oral sensory neurons of the geniculate ganglion (GG) innervate taste papillae and buds on the tongue and soft palate. Electrophysiological recordings of these neurons and fibers revealed complexity in the number of unique response profiles observed, suggesting there are several distinct neuronal subtypes. Molecular descriptions of these subpopulations are incomplete. We report here the identification of a subpopulation of GG oral sensory neurons in mice by expression of tyrosine hydroxylase (TH). TH-expressing geniculate neurons represent 10–20% of oral sensory neurons and these neurons innervate taste buds in fungiform and anterior foliate taste papillae on the surface of the tongue, as well as taste buds in the soft palate. While 35–50% of taste buds on the tongue are innervated by these TH+ neurons, 100% of soft palate taste buds are innervated. These neurons did not have extragemmal processes outside of taste buds and did not express the mechanosensory neuron-associated gene Ret, suggesting they are chemosensory and not somatosensory neurons. Within taste buds, TH-expressing fibers contacted both Type II and Type III cells, raising the possibility that they are responsive to more than one taste quality. During this analysis we also identified a rare TH+ taste receptor cell type that was found in only 12–25% of taste buds and co-expressed TRPM5, suggesting it was a Type II cell. Taken together, TH-expressing GG oral sensory neurons innervate taste buds preferentially in the soft palate and contact Type II and Type III taste bud receptor cells.

Development of Functional Properties in the Early Visual System: New Appreciations of the Roles of Lateral Geniculate Nucleus.

In the years following Hubel and Wiesel's first reports on ocular dominance plasticity and amblyopia, much attention has been focused on understanding the role of cortical circuits in developmental and experience-dependent plasticity. Initial studies found few differences between retinal ganglion cells and neurons in the lateral geniculate nucleus and uncovered little evidence for an impact of altered visual experience on the functional properties of lateral geniculate nucleus neurons. In the last two decades, however, studies have revealed that the connectivity between the retina and lateral geniculate nucleus is much richer than was previously appreciated, even revealing visual plasticity - including ocular dominance plasticity - in lateral geniculate nucleus neurons. Here we review the development of the early visual system and the impact of experience with a distinct focus on recent discoveries about lateral geniculate nucleus, its connectivity, and evidence for its plasticity and rigidity during development.

A CHAOTIC MULTILAYER LIF SCHEME TO MODEL THE PRIMARY VISUAL CORTEX

Precise mathematical modeling of the primary visual cortex (V1) is still a challenging problem. Due to the high similarity of visual system of cat and human, in this paper, we present a hybrid model to track the electrical responses of neurons that are measured by a multi-electrode array implanted in cat V1. The proposed model combines a stochastic phenomenological model with a multilayer leaky integrate-and-fire (LIF) model to predict V1 responses. Since all the existing visual cortex models do not capture the stochastic properties of synaptic changes, the proposed phenomenological model provides input currents for V1 by utilizing continuous chaotic neural equations with a quantization rule. Then a multilayer LIF model is presented to mimic the functions of lateral geniculate nucleus (LGN) and V1 neurons by their corresponding differential equations. The input current in these models is from the presynaptic neurons, which are computed using the LIF model. The LGN-V1 neuronal connections are adopted from previous studies, where the receptive fields (RFs) of LGN neurons converge onto elongated spatial structures that denote RFs of V1 neurons. The main purpose of this paper is to develop a short-term plasticity model that is more consistent with the nature of the LGN and V1 responses compared to state-of-the-art models. Previous studies have not incorporated the stochastic and quantized behaviors of neurons that in the recorded data of implemented electrodes. The experimental results show the ability of the proposed model to accurately predict spikes recorded experimentally, indicating the model outperforms the state-of-the-art method.

Single cell plasticity and population coding stability in auditory thalamus upon associative learning

Cortical and limbic brain areas are regarded as centres for learning. However, how thalamic sensory relays participate in plasticity upon associative learning, yet support stable long-term sensory coding remains unknown. Using a miniature microscope imaging approach, we monitor the activity of populations of auditory thalamus (medial geniculate body) neurons in freely moving mice upon fear conditioning. We find that single cells exhibit mixed selectivity and heterogeneous plasticity patterns to auditory and aversive stimuli upon learning, which is conserved in amygdala-projecting medial geniculate body neurons. Activity in auditory thalamus to amygdala-projecting neurons stabilizes single cell plasticity in the total medial geniculate body population and is necessary for fear memory consolidation. In contrast to individual cells, population level encoding of auditory stimuli remained stable across days. Our data identifies auditory thalamus as a site for complex neuronal plasticity in fear learning upstream of the amygdala that is in an ideal position to drive plasticity in cortical and limbic brain areas. These findings suggest that medial geniculate body’s role goes beyond a sole relay function by balancing experience-dependent, diverse single cell plasticity with consistent ensemble level representations of the sensory environment to support stable auditory perception with minimal affective bias.

Cell non-autonomous requirement of p75 in the development of geniculate oral sensory neurons

During development of the peripheral taste system, oral sensory neurons of the geniculate ganglion project via the chorda tympani nerve to innervate taste buds in fungiform papillae. Germline deletion of the p75 neurotrophin receptor causes dramatic axon guidance and branching deficits, leading to a loss of geniculate neurons. To determine whether the developmental functions of p75 in geniculate neurons are cell autonomous, we deleted p75 specifically in Phox2b + oral sensory neurons (Phox2b-Cre; p75fx/fx) or in neural crest-derived cells (P0-Cre; p75fx/fx) and examined geniculate neuron development. In germline p75−/− mice half of all geniculate neurons were lost. The proportion of Phox2b + neurons, as compared to Phox2b-pinna-projecting neurons, was not altered, indicating that both populations were affected similarly. Chorda tympani nerve recordings demonstrated that p75−/− mice exhibit profound deficits in responses to taste and tactile stimuli. In contrast to p75−/− mice, there was no loss of geniculate neurons in either Phox2b-Cre; p75fx/fx or P0-Cre; p75fx/fx mice. Electrophysiological analyses demonstrated that Phox2b-Cre; p75fx/fx mice had normal taste and oral tactile responses. There was a modest but significant loss of fungiform taste buds in Phox2b-Cre; p75fx/fx mice, although there was not a loss of chemosensory innervation of the remaining fungiform taste buds. Overall, these data suggest that the developmental functions of p75 are largely cell non-autonomous and require p75 expression in other cell types of the chorda tympani circuit.

Synchrony of Spontaneous Burst Firing between Retinal Ganglion Cells Across Species.

Neurons communicate with other neurons in response to environmental changes. Their goal is to transmit information to their targets reliably. A burst, which consists of multiple spikes within a short time interval, plays an essential role in enhancing the reliability of information transmission through synapses. In the visual system, retinal ganglion cells (RGCs), the output neurons of the retina, show bursting activity and transmit retinal information to the lateral geniculate neuron of the thalamus. In this study, to extend our interest to the population level, the burstings of multiple RGCs were simultaneously recorded using a multi-channel recording system. As the first step in network analysis, we focused on investigating the pairwise burst correlation between two RGCs. Furthermore, to assess if the population bursting is preserved across species, we compared the synchronized bursting of RGCs between marmoset monkey (callithrix jacchus), one species of the new world monkeys and mouse (C57BL/6J strain). First, monkey RGCs showed a larger number of spikes within a burst, while the inter-spike interval, burst duration, and inter-burst interval were smaller compared with mouse RGCs. Monkey RGCs showed a strong burst synchronization between RGCs, whereas mouse RGCs showed no correlated burst firing. Monkey RGC pairs showed significantly higher burst synchrony and mutual information than mouse RGC pairs did. Comprehensively, through this study, we emphasize that two species have a different bursting activity of RGCs and different burst synchronization suggesting two species have distinctive retinal processing.

Orexin A as a modulator of dorsal lateral geniculate neuronal activity: a comprehensive electrophysiological study on adult rats

Orexins (OXA, OXB) are hypothalamic peptides playing crucial roles in arousal, feeding, social and reward-related behaviours. A recent study on juvenile rats suggested their involvement in vision modulation due to their direct action on dorsal lateral geniculate (dLGN) neurons. The present study aimed to verify whether a similar action of OXA can be observed in adulthood. Thus, in vivo and in vitro electrophysiological recordings on adult Wistar rats across light-dark and cortical cycles were conducted under urethane anaesthesia. OXA influenced ~28% of dLGN neurons recorded in vivo by either excitation or suppression of neuronal firing. OXA-responsive neurons did not show any spatial distribution nor represent a coherent group of dLGN cells, and responded to OXA similarly across the light–dark cycle. Interestingly, some OXA-responsive neurons worked in a cortical state-dependent manner, especially during the dark phase, and ‘preferred’ cortical activation over slow-wave activity induced by urethane. The corresponding patch clamp study confirmed these results by showing that < 20% of dLGN neurons were excited by OXA under both light regimes. The results suggest that OXA is involved in the development of the visual system rather than in visual processes and further implicate OXA in the mediation of circadian and arousal-related activity.

Altered oscillation frequencies in the lateral geniculate complex in the rat model of absence epilepsy

Absence epilepsy (AE) is a neurological disease that manifests in spike-wave discharges not present in healthy neuronal circuits. Mutations in ion channels directly underlying this rhythmic discharge may additionally affect rhythms in multiple brain centres which disturbances contribute to the epileptic phenotype. Malfunctioning of the light detection system (from retina to subcortical visual structures), heavily dependent on oscillatory activities, could partially explain severe problems with sleep and arousal observed in epileptic patients. Therefore, the aim of our study was to evaluate characteristics of retinal-derived oscillations in the lateral geniculate complex of the thalamus; a major gateway for the light information flow for the brain. Extracellular recordings in vivo were performed on urethane-anaesthetised WAG/Rij and Wistar rats from single units in the identified parts of lateral geniculate complex to test their basic oscillatory features as well as reaction to transient and sustained changes in ambient light conditions. Here, we show altered rhythmic activity of the lateral geniculate neurons in the absence epilepsy model with the increase of both the infra-slow and fast oscillatory frequencies. Further, we describe their disturbed reaction to sustain change in ambient light and provide evidence for major changes in the intergeniculate leaflet neuronal firing; a part of the lateral geniculate complex implicated in the circadian timekeeping. Altogether, our results are the first to show a malfunctioning of light detection mechanisms in the absence epilepsy that may in turn underpin sleep-promoting system insufficiencies and other arousal disturbances contributing to epileptic phenotype.

TrkB expression and dependence divides gustatory neurons into three subpopulations

BackgroundDuring development, gustatory (taste) neurons likely undergo numerous changes in morphology and expression prior to differentiation into maturity, but little is known this process or the factors that regulate it. Neuron differentiation is likely regulated by a combination of transcription and growth factors. Embryonically, most geniculate neuron development is regulated by the growth factor brain derived neurotrophic factor (BDNF). Postnatally, however, BDNF expression becomes restricted to subpopulations of taste receptor cells with specific functions. We hypothesized that during development, the receptor for BDNF, tropomyosin kinase B receptor (TrkB), may also become developmentally restricted to a subset of taste neurons and could be one factor that is differentially expressed across taste neuron subsets.MethodsWe used transgenic mouse models to label both geniculate neurons innervating the oral cavity (Phox2b+), which are primarily taste, from those projecting to the outer ear (auricular neurons) to label TrkB expressing neurons (TrkBGFP). We also compared neuron number, taste bud number, and taste receptor cell types in wild-type animals and conditional TrkB knockouts.ResultsBetween E15.5-E17.5, TrkB receptor expression becomes restricted to half of the Phox2b + neurons. This TrkB downregulation was specific to oral cavity projecting neurons, since TrkB expression remained constant throughout development in the auricular geniculate neurons (Phox2b-). Conditional TrkB removal from oral sensory neurons (Phox2b+) reduced this population to 92% of control levels, indicating that only 8% of these neurons do not depend on TrkB for survival during development. The remaining neurons failed to innervate any remaining taste buds, 14% of which remained despite the complete loss of innervation. Finally, some types of taste receptor cells (Car4+) were more dependent on innervation than others (PLCβ2+).ConclusionsTogether, these findings indicate that TrkB expression and dependence divides gustatory neurons into three subpopulations: 1) neurons that always express TrkB and are TrkB-dependent during development (50%), 2) neurons dependent on TrkB during development but that downregulate TrkB expression between E15.5 and E17.5 (41%), and 3) neurons that never express or depend on TrkB (9%). These TrkB-independent neurons are likely non-gustatory, as they do not innervate taste buds.

Commissural communication allows mouse intergeniculate leaflet and ventral lateral geniculate neurons to encode interocular differences in irradiance.

Key points Unlike other visual thalamic regions, the intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/vLGN) possess extensive reciprocal commissural connections, the functions of which are unknown.Using electrophysiological approaches, it is shown that commissural projecting IGL/vLGN cells are primarily activated by light increments to the contralateral eye while cells receiving commissural input typically exhibit antagonistic binocular responses.Across antagonistic cells, the nature of the commissural input (excitatory or inhibitory) corresponds to the presence of ipsilateral ON or OFF visual responses and in both cases antagonistic responses disappear following inactivation of the contralateral thalamus.The steady state firing rates of antagonistic cells uniquely encode interocular differences in irradiance.There is a pivotal role for IGL/vLGN commissural signalling in generating new sensory properties that are potentially useful for the proposed contributions of these nuclei to visuomotor/vestibular and circadian control. The intergeniculate leaflet and ventral lateral geniculate nucleus (IGL/vLGN) are portions of the visual thalamus implicated in circadian and visuomotor/vestibular control. A defining feature of IGL/vLGN organisation is the presence of extensive reciprocal commissural connections, the functions of which are at present unknown. Here we use a combination of multielectrode recording, electrical microstimulation, thalamic inactivation and a range of visual stimuli in mice to address this deficit. Our data indicate that, like most IGL/vLGN cells, those that project commissurally primarily convey contralateral ON visual signals while most IGL/vLGN neurons that receive this input exhibit antagonistic binocular responses (i.e. excitatory responses driven by one eye and inhibitory responses driven by the other), enabling them to encode interocular differences in irradiance. We also confirm that this property derives from commissural input since, following inactivation of the contralateral visual thalamus, these cells instead display monocular contralateral‐driven ON responses. Our data thereby reveal a fundamental role for commissural signalling in generating new visual response properties at the level of the visual thalamus.

Adenosine A1 Receptor mRNA Expression by Neurons and Glia in the Auditory Forebrain.

ABSTRACTIn the brain, purines such as ATP and adenosine can function as neurotransmitters and co‐transmitters, or serve as signals in neuron–glial interactions. In thalamocortical (TC) projections to sensory cortex, adenosine functions as a negative regulator of glutamate release via activation of the presynaptic adenosine A1 receptor (A1R). In the auditory forebrain, restriction of A1R‐adenosine signaling in medial geniculate (MG) neurons is sufficient to extend LTP, LTD, and tonotopic map plasticity in adult mice for months beyond the critical period. Interfering with adenosine signaling in primary auditory cortex (A1) does not contribute to these forms of plasticity, suggesting regional differences in the roles of A1R‐mediated adenosine signaling in the forebrain. To advance understanding of the circuitry, in situ hybridization was used to localize neuronal and glial cell types in the auditory forebrain that express A1R transcripts (Adora1), based on co‐expression with cell‐specific markers for neuronal and glial subtypes. In A1, Adora1 transcripts were concentrated in L3/4 and L6 of glutamatergic neurons. Subpopulations of GABAergic neurons, astrocytes, oligodendrocytes, and microglia expressed lower levels of Adora1. In MG, Adora1 was expressed by glutamatergic neurons in all divisions, and subpopulations of all glial classes. The collective findings imply that A1R‐mediated signaling broadly extends to all subdivisions of auditory cortex and MG. Selective expression by neuronal and glial subpopulations suggests that experimental manipulations of A1R‐adenosine signaling could impact several cell types, depending on their location. Strategies to target Adora1 in specific cell types can be developed from the data generated here. Anat Rec, 301:1882–1905, 2018. © 2018 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.

Autophosphorylated CaMKII Facilitates Spike Propagation in Rat Optic Nerve.

Repeated spike firing can transmit information at synapses and modulate spike timing, shape, and conduction velocity. These latter effects have been found to result from voltage-induced changes in ion currents and could alter the signals carried by axons. Here, we test whether Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates spike propagation in adult rat optic nerve. We find that small-, medium-, and large-diameter axons bind anti-Thr286-phosphorylated CaMKII (pT286) antibodies and that, in isolated optic nerves, electrical stimulation reduces pT286 levels, spike propagation is hastened by CaMKII autophosphorylation and slowed by CaMKII dephosphorylation, single and multiple spikes slow propagation of subsequently activated spikes, and more frequent stimulation produces greater slowing. Likewise, exposing freely moving animals to flickering illumination reduces pT286 levels in optic nerves and electrically eliciting spikes in vivo in either the optic nerve or optic chiasm slows subsequent spike propagation in the optic nerve. By increasing the time that elapses between successive spikes as they propagate, pT286 dephosphorylation and activity-induced spike slowing reduce the frequency of propagated spikes below the frequency at which they were elicited and would thus limit the frequency at which axons synaptically drive target neurons. Consistent with this, the ability of retinal ganglion cells to drive at least some lateral geniculate neurons has been found to increase when presented with light flashes at low and moderate temporal frequencies but less so at high frequencies. Activity-induced decreases in spike frequency may also reduce the energy required to maintain normal intracellular Na+ and Ca2+ levels.SIGNIFICANCE STATEMENT By propagating along axons at constant velocities, spikes could drive synapses as frequently as they are initiated. However, the onset of spiking has been found to alter the conduction velocity of subsequent ("follower") spikes in various preparations. Here, we find that spikes reduce spike frequency in rat optic nerve by slowing follower spike propagation and that electrically stimulated spiking ex vivo and spike-generating flickering illumination in vivo produce net decreases in axonal Ca2+/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation. Consistent with these effects, propagation speed increases and decreases, respectively, with CaMKII autophosphorylation and dephosphorylation. Lowering spike frequency by CaMKII dephosphorylation is a novel consequence of axonal spiking and light adaptation that could decrease synaptic gain as stimulus frequency increases and may also reduce energy use.

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

Experience-dependent plasticity in the mature visual system is widely considered to be cortical. Using chronic two-photon Ca2+ 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 GABAA receptor agonist muscimol. Our data suggest that OD shifts observed in the binocular visual cortex of adult mice may at least partially reflect plasticity of eye-specific inputs onto dLGN neurons.

Medial geniculate neurons show diverse effects in response to electrical stimulation of prefrontal cortex

Phantom perceptions have been proposed to arise due to dysfunctional sensory gating at the level of the thalamus. Recently, it has been suggested that tinnitus, a phantom perception of sound, may arise from altered cortico-limbic circuitry and its connection with the auditory thalamus, the medial geniculate nucleus (MGN). Indeed, some elements of this cortico-limbic circuitry, such as the prefrontal cortex (PFC), as well as elements of the auditory pathway, have been shown to be altered in humans with tinnitus. However, the functional connectivity between PFC and MGN has not yet been explored. We therefore investigated the effects of activation of the PFC on neuronal activity in MGN in normal anaesthetized Wistar rats. Bipolar electrical stimulation was delivered to the PFC while recording single neuron activity in the MGN. The majority (81%) of MGN neurons sampled showed a change in their spontaneous firing rate in response to electrical stimulation of the PFC. The effects observed varied greatly between neurons and included combinations of inhibitory and excitatory effects with a wide range of latencies. The effects were not dependent on acoustic response type or MGN subdivision. These data demonstrate that PFC activation can modulate MGN neuronal activity and this connection could potentially play a role in sensory gating of auditory signals.

A ganglion-cell-based primary image representation method and its contribution to object recognition

ABSTRACTA visual stimulus is represented by the biological visual system at several levels: in the order from low to high levels, they are: photoreceptor cells, ganglion cells (GCs), lateral geniculate nucleus cells and visual cortical neurons. Retinal GCs at the early level need to represent raw data only once, but meet a wide number of diverse requests from different vision-based tasks. This means the information representation at this level is general and not task-specific. Neurobiological findings have attributed this universal adaptation to GCs' receptive field (RF) mechanisms. For the purposes of developing a highly efficient image representation method that can facilitate information processing and interpretation at later stages, here we design a computational model to simulate the GC's non-classical RF. This new image presentation method can extract major structural features from raw data, and is consistent with other statistical measures of the image. Based on the new representation, the performances of other state-of-the-art algorithms in contour detection and segmentation can be upgraded remarkably. This work concludes that applying sophisticated representation schema at early state is an efficient and promising strategy in visual information processing.

Enforced DNA repair enzymes rescue neurons from apoptosis induced by target deprivation and axotomy in mouse models of neurodegeneration

It is unknown whether DNA damage accumulation is an upstream instigator or secondary effect of the cell death process in different populations of adult postmitotic neurons in the central nervous system. In two different mouse models of injury-induced neurodegeneration characterized by relatively synchronous accumulation of mitochondria, oxidative stress, and DNA damage prior to neuronal apoptosis, we enforced the expression of human 8-oxoguanine DNA glycosylase (hOGG1) and human apurinic-apyrimidinic endonuclease-1/Ref1 (hAPE) using recombinant adenoviruses (Ad). Thalamic lateral geniculate neurons and lumbar spinal cord motor neurons were transduced by Ad-hOGG1 and Ad-hAPE injections into the occipital cortex and skeletal muscle, respectively, prior to their target deprivation- and axotomy-induced retrograde apoptosis. Enforced expression of hOGG1 and hAPE in thalamus and spinal cord was confirmed by western blotting and immunohistochemistry. In injured populations of neurons in thalamus and spinal cord, a DNA damage response (DDR) was registered, as shown by localization of phospho-activated p53, Rad17, and replication protein A-32 immunoreactivities, and this DDR was attenuated more effectively by enforced hAPE expression than by hOGG1 expression. Enforced expression of hOGG1 and hAPE significantly protected thalamic neurons and motor neurons from retrograde apoptosis induced by target deprivation and axotomy. We conclude that a DDR response is engaged pre-apoptotically in different types of injured mature CNS neurons and that DNA repair enzymes can regulate the survival of retrogradely dying neurons, suggesting that DNA damage and activation of DDR are upstream mechanisms for this form of adult neurodegeneration in vivo, thus identifying DNA repair as a therapeutic target for neuroprotection.

Role of BDNF in the taste system

Neurotrophins are a family of proteins that regulate neural survival, development, function and plasticity in the central and the peripheral nervous system. There are four neurotrophins: NGF, BDNF, NT-3 and NT-4. Among them, BDNF is mostly studied in the taste system due to its high expression. Recent studies have shown BDNF play an important role in the developmental and mature taste system, by regulating survival of taste cells and geniculate ganglion neurons, and maintaining and guiding taste nerve innervations. These studies imply BDNF has great potentialities for therapeutic usage to enhance sensory regeneration following nerve injury, with aging, and in some neurodegenerative diseases.

Refinement of the Retinogeniculate Synapse by Bouton Clustering

Mammalian sensory circuits become refined over development in an activity-dependent manner. Retinal ganglion cell (RGC) axons from each eye first map to their target in the geniculate and then segregate into eye-specific layers by the removal and addition of axon branches. Once segregation is complete, robust functional remodeling continues as the number of afferent inputs to each geniculate neuron decreases from many to a few. It is widely assumed that large-scale axon retraction underlies this later phase of circuit refinement. On the contrary, RGC axons remain stable during functional pruning. Instead, presynaptic boutons grow in size and cluster during this process. Moreover, they exhibit dynamic spatial reorganization in response to sensory experience. Surprisingly, axon complexity decreases only after the completion of the thalamic critical period. Therefore, dynamic bouton redistribution along a broad axon backbone represents an unappreciated form of plasticity underlying developmental wiring and rewiring in the CNS.