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lateral geniculate nucleus [keywords]
- Acute effects of brexpiprazole on serotonin, dopamine, and norepinephrine systems: an in vivo electrophysiological characterization. [JOURNAL ARTICLE]
- J Pharmacol Exp Ther 2014 Sep 15.
Brexpiprazole, a compound sharing structural molecular characteristics with aripiprazole, is currently under investigation for the treatment of schizophrenia and depression. Using electrophysiological techniques, the present study assessed the in vivo action of brexpiprazole on serotonin (5-HT)1A, 5-HT1B, 5-HT2A receptor subtypes, dopamine (DA) D2 autoreceptors, and α1- and α2-adrenergic receptors. In addition, the effects on 5-HT1A autoreceptors in the dorsal raphe nucleus (DRN) and D2 autoreceptors in the ventral tegmental area (VTA) were compared to those of aripiprazole, an agent in wide clinical use. In the DRN, brexpiprazole completely inhibited the firing of 5-HT neurons via 5-HT1A agonism, and was more potent than aripiprazole (ED50=230 and 700 μg/kg, respectively). In the locus coeruleus, brexpiprazole reversed the inhibitory effect of the preferential 5-HT2A receptor agonist DOI on norepinephrine neuronal firing (ED50=110 μg/kg), demonstrating 5-HT2A antagonistic action. Brexpiprazole reversed the inhibitory effect of the DA agonist apomorphine on VTA DA neurons (ED50=61 μg/kg), whereas it was ineffective when administered alone, indicating partial agonistic action on D2 receptors. Compared to aripiprazole, which significantly inhibited the firing activity of VTA DA neurons, brexpiprazole displayed less efficacy at D2 receptors. In the hippocampus, brexpiprazole acted as a full agonist at 5-HT1A receptors on pyramidal neurons. Furthermore, it increased 5-HT release by terminal α2-adrenergic heteroceptor but not 5-HT1B autoreceptor antagonism. In the lateral geniculate nucleus, brexpiprazole displayed α1B-adrenoceptor antagonistic action. Taken together, these results provide insight in the in vivo action of brexpiprazole on monoamine targets relevant in the treatment of depression and schizophrenia.
- Heat shock protein 72 confers protection in retinal ganglion cells and lateral geniculate nucleus neurons via blockade of the SAPK/JNK pathway in a chronic ocular-hypertensive rat model. [Journal Article]
- Neural Regen Res 2014 Jul 15; 9(14):1395-401.
Optic nerve transection increased the expression of heat shock protein 72 (HSP72) in the lateral geniculate body, indicating that this protein is involved in the prevention of neuronal injury. Zinc sulfate and quercetin induced and inhibited the expression of HSP72, respectively. Intraperitoneal injections of zinc sulfate, SP600125 (c-Jun N-terminal kinase inhibitor), or quercetin were performed on retinal ganglion cells in a Wistar rat model of chronic ocular hypertension. Our results showed that compared with the control group, the expression of HSP72 in retinal ganglion cells and the lateral geniculate body was increased after the injection of zinc sulfate, but was decreased after the injection of quercetin. The expression of phosphorylated c-Jun N-terminal kinases and phosphorylated c-Jun were visible 3 days after injection in the control group, and reached a peak at 7 days. Zinc sulfate and SP600125 significantly decreased the expression of p-c-Jun, whereas quercetin significantly enhanced the expression of this protein. These results suggest that HSP72 protects retinal ganglion cells and lateral geniculate body in a rat model of chronic ocular hypertension from injury by blocking the activation of the stress-activated kinase/c-Jun N-terminal kinase apoptotic pathway.
- T-type calcium channels promote predictive homeostasis of input-output relations in thalamocortical neurons of lateral geniculate nucleus. [Journal Article]
- Front Comput Neurosci 2014.:98.
A general theory views the function of all neurons as prediction, and one component of this theory is that of "predictive homeostasis" or "prediction error." It is well established that sensory systems adapt so that neuronal output maintains sensitivity to sensory input, in accord with information theory. Predictive homeostasis applies the same principle at the cellular level, where the challenge is to maintain membrane excitability at the optimal homeostatic level so that spike generation is maximally sensitive to small gradations in synaptic drive. Negative feedback is a hallmark of homeostatic mechanisms, as exemplified by depolarization-activated potassium channels. In contrast, T-type calcium channels exhibit positive feedback that appears at odds with the theory. In thalamocortical neurons of lateral geniculate nucleus (LGN), T-type channels are capable of causing bursts of spikes with an all-or-none character in response to excitation from a hyperpolarized potential. This "burst mode" would partially uncouple visual input from spike output and reduce the information spikes convey about gradations in visual input. However, past observations of T-type-driven bursts may have resulted from unnaturally high membrane excitability. Here we have mimicked within rat brain slices the patterns of synaptic conductance that occur naturally during vision. In support of the theory of predictive homeostasis, we found that T-type channels restored excitability toward its homeostatic level during periods of hyperpolarization. Thus, activation of T-type channels allowed two retinal input spikes to cause one output spike on average, and we observed almost no instances in which output count exceeded input count (a "burst"). T-type calcium channels therefore help to maintain a single optimal mode of transmission rather than creating a second mode. More fundamentally our results support the general theory, which seeks to predict the properties of a neuron's ion channels and synapses given knowledge of natural patterns of synaptic input.
- [Cellular and molecular mechanisms of synapse elimination in the Mammalian brain]. [English Abstract, Journal Article]
- Brain Nerve 2014 Sep; 66(9):1069-77.
Abstract Neurons form exuberant synapses with target cells early in development. Then, necessary synapses are strengthened whereas unnecessary connections are weakened and eventually eliminated during postnatal development. This process, known as synapse elimination, is widely believed to be a crucial step for shaping immature neural circuits into functionally mature versions. In the neonatal mouse cerebellum, each Purkinje cell is innervated by multiple climbing fibers (CFs). Their synaptic strengths are initially uniform but a single CF strengthens relative to the other CFs during the first postnatal week. Then the weaker CFs are eliminated during the second postnatal week. Similar developmental changes occur in several other synapses including the neuromuscular junction and the projection from the retina to the lateral geniculate nucleus (LGN). Recent studies have clarified that synapse elimination consists of multiple phases that involve distinct types of neural activity and/or molecular mechanisms.
- Supraspinal gene transfer by intrathecal adeno-associated virus serotype 5. [Journal Article]
- Front Neuroanat 2014.:66.
We report the pattern of transgene expression across brain regions after intrathecal delivery of adeno-associated virus serotype 5 (AAV5). Labeling in hindbrain appeared to be primarily neuronal, and was detected in sensory nuclei of medulla, pontine nuclei, and all layers of cerebellar cortex. Expression in midbrain was minimal, and generally limited to isolated neurons and astrocytes in the cerebral peduncles. GFP immunoreactivity (-ir) in thalamus was most prominent in medial geniculate nucleus, and otherwise limited to posterior nuclei of the dorsal and lateral margins. Labeling was also observed in neurons and astrocytes of the hippocampal formation and amygdaloid complex. In the hippocampal formation, GFP-ir was found in neuronal cell bodies of the rostral ventral portion, but was largely restricted to fiber-like staining in the molecular layer of dentate gyrus and stratum lacunosum-moleculare of the rostral dorsal region. GFP-ir was seen in neurons and astroglia throughout caudal cortex, whereas in rostral regions of neocortex it was limited to isolated neurons and non-neuronal cells. Labeling was also present in olfactory bulb. These results demonstrate that intrathecal delivery of AAV5 vector leads to transgene expression in discrete CNS regions throughout the rostro-caudal extent of the neuraxis. A caudal-to-rostral gradient of decreasing GFP-ir was present in choroid plexus and Purkinje cells, suggesting that spread of virus through cerebrospinal fluid plays a role in the resulting transduction pattern. Other factors contributing to the observed expression pattern likely include variations in cell-surface receptors and inter-parenchymal space.
- Response features across the auditory midbrain reveal an organization consistent with a dual lemniscal pathway. [Journal Article]
- J Neurophysiol 2014 Aug 15; 112(4):981-98.
The central auditory system has traditionally been divided into lemniscal and nonlemniscal pathways leading from the midbrain through the thalamus to the cortex. This view has served as an organizing principle for studying, modeling, and understanding the encoding of sound within the brain. However, there is evidence that the lemniscal pathway could be further divided into at least two subpathways, each potentially coding for sound in different ways. We investigated whether such an interpretation is supported by the spatial distribution of response features in the central nucleus of the inferior colliculus (ICC), the part of the auditory midbrain assigned to the lemniscal pathway. We recorded responses to pure tone stimuli in the ICC of ketamine-xylazine-anesthetized guinea pigs and used three-dimensional brain reconstruction techniques to map the location of the recording sites. Compared with neurons in caudal-and-medial regions within an isofrequency lamina of the ICC, neurons in rostral-and-lateral regions responded with shorter first-spike latencies with less spiking jitter, shorter durations of spiking responses, a higher proportion of spikes occurring near the onset of the stimulus, lower thresholds, and larger local field potentials with shorter latencies. Further analysis revealed two distinct clusters of response features located in either the caudal-and-medial or the rostral-and-lateral parts of the isofrequency laminae of the ICC. Thus we report substantial differences in coding properties in two regions of the ICC that are consistent with the hypothesis that the lemniscal pathway is made up of at least two distinct subpathways from the midbrain up to the cortex.
- NMDA Spike/Plateau Potentials in Dendrites of Thalamocortical Neurons. [Journal Article]
- J Neurosci 2014 Aug 13; 34(33):10892-905.
Dendritic NMDA spike/plateau potentials, first discovered in cortical pyramidal neurons, provide supralinear integration of synaptic inputs on thin and distal dendrites, thereby increasing the impact of these inputs on the soma. The more specific functional role of these potentials has been difficult to clarify, partly due to the complex circuitry of cortical neurons. Thalamocortical (TC) neurons in the dorsal lateral geniculate nucleus participate in simpler circuits. They receive their primary afferent input from retina and send their output to visual cortex. Cortex, in turn, regulates this output through massive feedback to distal dendrites of the TC neurons. The TC neurons can operate in two modes related to behavioral states: burst mode prevailing during sleep, when T-type calcium bursts largely disrupt the transfer of signals from retina to cortex, and tonic mode, which provides reliable transfer of retinal signals to cortex during wakefulness. We studied dendritic potentials in TC neurons with combined two-photon calcium imaging and whole-cell recording of responses to local dendritic glutamate iontophoresis in acute brain slices from mice. We found that NMDA spike/plateaus can be elicited locally at distal dendrites of TC neurons. We suggest that these dendritic potentials have important functions in the cortical regulation of thalamocortical transmission. NMDA spike/plateaus can induce shifts in the functional mode from burst to tonic by blockade of T-type calcium conductances. Moreover, in tonic mode, they can facilitate the transfer of retinal signals to cortex by depolarization of TC neurons.
- Learning-Related Neuronal Activity in the Ventral Lateral Geniculate Nucleus during Assocaitive Cerebellar Learning. [JOURNAL ARTICLE]
- J Neurophysiol 2014 Aug 13.
During delay eyeblink conditioning rats learn to produce an eyelid closure conditioned response (CR) to a conditioned stimulus (CS) such as a light that precedes and co-terminates with an unconditioned stimulus (US). Previous studies have suggested that the ventral lateral geniculate nucleus (LGNv) might play an important role in visual eyeblink conditioning by supplying visual sensory input to the pontine nuclei (PN) and also receiving feedback from the cerebellum. No prior study has investigated LGNv neuronal activity during eyeblink conditioning. The present study used multiple tetrodes to monitor single-unit activity in the rat LGNv during pre-exposure (CS only), unpaired CS/US, and paired CS-US training conditions. This behavioral training sequence was used to investigate non-associative and associative driven neuronal activity in the LGNv during training. LGNv neuronal activity habituated during unpaired training and then recovered from habituation during subsequent paired training, which may indicate that the LGNv plays a role in attention to the CS. The amplitude of LGNv neuronal activity correlated with CR production during paired but not unpaired CS/US training. Cerebellar feedback to the LGNv may play a role in modulating LGNv activity and attention to the CS during paired training. Based on the present findings, we hypothesize that LGNv's role in visual eyeblink conditioning goes beyond simply routing visual CS information to the PN and involves modulation of attention.
- Lateral geniculate body evoked potentials elicited by visual and electrical stimulation. [Journal Article]
- Korean J Ophthalmol 2014 Aug; 28(4):337-42.
Blind individuals who have photoreceptor loss are known to perceive phosphenes with electrical stimulation of their remaining retinal ganglion cells. We proposed that implantable lateral geniculate body (LGB) stimulus electrode arrays could be used to generate phosphene vision. We attempted to refine the basic reference of the electrical evoked potentials (EEPs) elicited by microelectrical stimulations of the optic nerve, optic tract and LGB of a domestic pig, and then compared it to visual evoked potentials (VEPs) elicited by short-flash stimuli.For visual function measurement, VEPs in response to short-flash stimuli on the left eye of the domestic pig were assessed over the visual cortex at position Oz with the reference electrode at Fz. After anesthesia, linearly configured platinum wire electrodes were inserted into the optic nerve, optic track and LGB. To determine the optimal stimulus current, EEPs were recorded repeatedly with controlling the pulse and power. The threshold of current and charge density to elicit EEPs at 0.3 ms pulse duration was about ±10 µA.Our experimental results showed that visual cortex activity can be effectively evoked by stimulation of the optic nerve, optic tract and LGB using penetrating electrodes. The latency of P1 was more shortened as the electrical stimulation was closer to LGB. The EEPs of two-channel in the visual cortex demonstrated a similar pattern with stimulation of different spots of the stimulating electrodes. We found that the LGB-stimulated EEP pattern was very similar to the simultaneously generated VEP on the control side, although implicit time deferred.EEPs and VEPs derived from visual-system stimulation were compared. The LGB-stimulated EEP wave demonstrated a similar pattern to the VEP waveform except implicit time, indicating prosthetic-based electrical stimulation of the LGB could be utilized for the blind to perceive vision of phosphenes.
- Subcollicular projections to the auditory thalamus and collateral projections to the inferior colliculus. [Journal Article]
- Front Neuroanat 2014.:70.
Experiments in several species have identified direct projections to the medial geniculate nucleus (MG) from cells in subcollicular auditory nuclei. Moreover, many cochlear nucleus cells that project to the MG send collateral projections to the inferior colliculus (IC) (Schofield et al., 2014). We conducted three experiments to characterize projections to the MG from the superior olivary and the lateral lemniscal regions in guinea pigs. For experiment 1, we made large injections of retrograde tracer into the MG. Labeled cells were most numerous in the superior paraolivary nucleus, ventral nucleus of the trapezoid body, lateral superior olivary nucleus, ventral nucleus of the lateral lemniscus, ventrolateral tegmental nucleus, paralemniscal region and sagulum. Additional sources include other periolivary nuclei and the medial superior olivary nucleus. The projections are bilateral with an ipsilateral dominance (66%). For experiment 2, we injected tracer into individual MG subdivisions. The results show that the subcollicular projections terminate primarily in the medial MG, with the dorsal MG a secondary target. The variety of projecting nuclei suggest a range of functions, including monaural and binaural aspects of hearing. These direct projections could provide the thalamus with some of the earliest (i.e., fastest) information regarding acoustic stimuli. For experiment 3, we made large injections of different retrograde tracers into one MG and the homolateral IC to identify cells that project to both targets. Such cells were numerous and distributed across many of the nuclei listed above, mostly ipsilateral to the injections. The prominence of the collateral projections suggests that the same information is delivered to both the IC and the MG, or perhaps that a common signal is being delivered as a preparatory indicator or temporal reference point. The results are discussed from functional and evolutionary perspectives.