Thalamus & related systems最新文献

It has been conclusively demonstrated in juvenile rodents that the inhibitory neurons of the nucleus reticularis thalami (NRT) communicate with each other via connexin 36 (Cx36)-based electrical synapses. However, whether functional electrical synapses persist into adulthood is not fully known. Here we show that in the presence of the metabotropic glutamate receptor (mGluR) agonists, trans-ACPD (100 muM) or DHPG (100 muM), 15% of neurons in slices of the adult cat NRT maintained in vitro exhibit stereotypical spikelets with several properties that indicate that they reflect action potentials that have been communicated through an electrical synapse. In particular, these spikelets, i) display a conserved all-or-nothing waveform with a pronounced after-hyperpolarization (AHP), ii) exhibit an amplitude and time to peak that are unaffected by changes in membrane potential, iii) always occur rhythmically with the precise frequency increasing with depolarization, and iv) are resistant to blockers of conventional, fast chemical synaptic transmission. Thus, these results indicate that functional electrical synapses in the NRT persist into adulthood where they are likely to serve as an effective synchronizing mechanism for the wide variety of physiological and pathological rhythmic activities displayed by this nucleus.

Anterior thalamic lesions are thought to produce 'covert pathology' in retrosplenial cortex, but the causes are unknown. Microarray analyses tested the hypothesis that thalamic damage causes a chronic, hypo-function of metabolic and plasticity-related pathways (Experiment 1). Rats with unilateral, anterior thalamic lesions were exposed to a novel environment for 20 minutes, and granular retrosplenial tissue sampled from both hemispheres 30 minutes, 2h, or 8h later. Complementary statistical approaches (analyses of variance, predictive patterning and gene set enrichment analysis) revealed pervasive gene expression differences between retrosplenial cortex ipsilateral to the thalamic lesion and contralateral to the lesion. Selected gene differences were validated by QPCR, immunohistochemistry (Experiment 1), and in situ hybridisation (Experiment 2). Following thalamic lesions, the retrosplenial cortex undergoes profuse cellular transcriptome changes including lower relative levels of specific mRNAs involved in energy metabolism and neuronal plasticity. These changes in functional gene expression may be largely driven by decreases in the expression of multiple transcription factors, including brd8, c-fos, fra-2, klf5, nfix, nr4a1, smad3, smarcc2, and zfp9, with a much smaller number (nfat5, neuroD1, RXRγ) showing increases. These findings have implications for conditions such as diencephalic amnesia and Alzheimer's disease, where both anterior thalamic pathology and retrosplenial cortex hypometabolism are prominent.

The work of Mircea Steriade demonstrated that the neocortex could synchronize large regions of the thalamus within 10-100 milliseconds (for review see Steriade and Timofeev, 2003, Steriade, 2005). Unlike the synchrony generated by the cortex, the retinal afferents synchronize a restricted group of neighboring thalamic neurons with <1-millisecond precision (Alonso et al., 1996, Yeh et al., 2003). Here, we use a large sample (n= 372) of simultaneous recordings from neighboring neurons in the Lateral Geniculate Nucleus (LGN) to illustrate the high specificity of the synchrony generated by retinal afferents and its dependency on sensory stimulation. First, we demonstrate that cells sharing a retinal afferent show a balanced receptive field diversity: while slight receptive field mismatches are common, the largest mismatches in a specific property (e.g. receptive field size) are restricted to cells that are precisely matched in other properties (e.g. receptive field overlap). Second, we show that these receptive field mismatches are functionally important and can lead to a 5-fold variation in the percentage of synchronous spikes driven by the shared retinal afferent under different stimulus conditions. Based on these and other findings, we speculate that the precise synchronous firing of cells sharing a retinal afferent could serve to amplify local stimuli that may be too brief and small to generate a large number of thalamic spikes.

Both the thalamocortical and limbic systems generate a variety of brain state-dependent rhythms but the relationship between the oscillatory families is not well understood. Transfer of information across structures can be controlled by the offset oscillations. We suggest that slow oscillation of the neocortex, which was discovered by Mircea Steriade, temporally coordinates the self-organized oscillations in the neocortex, entorhinal cortex, subiculum and hippocampus. Transient coupling between rhythms can guide bidirectional information transfer among these structures and might serve to consolidate memory traces.

We studied circuit activities in layer IV of rat somatosensory barrel cortex containing microgyri induced by neonatal freeze lesions. Structural abnormalities in GABAergic interneurons are present in the epileptogenic paramicrogyral area (PMG) and we therefore tested the hypothesis that decreased postsynaptic inhibition within barrel microcircuits occurs in the PMG and contributes to epileptogenesis when thalamocortical afferents are activated. In thalamocortical (TC) slices from naïve animals, single electrical stimuli within the thalamic ventrobasal (VB) nucleus evoked transient cortical multi-unit activity lasting 65±42 ms. Similar stimuli in TC slices from lesioned barrel cortex elicited prolonged 850 ±100 ms paroxysmal discharges that originated in the PMG and propagated laterally over several mm. Paroxysmal discharges were shortened in duration by ~70 % when APV was applied, and were totally abolished by CNQX. The cortical paroxysmal discharges did not evoke thalamic oscillations. Whole cell patch clamp recordings showed that there was a shift in the balance of TC evoked responses in the PMG that favored excitation over inhibition. Dual whole-cell recordings in layer IV of the PMG indicated that there was selective loss of inhibition from fast-spiking interneurons to spiny neurons in the barrel circuits that likely contributed to unconstrained cortical recurrent excitation with generation and spread of paroxysmal discharges.

The Eph family of receptor tyrosine kinases and their partner ligands, the ephrins, mediate cell-cell interactions in the developing nervous system. Signaling events between Eph receptors and ephrin ligands on interacting cells affect the growth, maturation, migration and connectivity of individual neurons and neural networks. Here we review the known roles of Eph-ephrin signaling in the development of the thalamus and its connections, and pose new questions for experimental study.

The transcriptional mechanisms governing the development and plasticity of somatopic sensory maps in the cerebral cortex have not been extensively studied. In particular, no studies have addressed the role of epigenetic mechanisms in the development of sensory maps. DNA methylation is one the main epigenetic mechanisms available to mammalian cells to regulate gene transcription. As demethylation results in embryonic lethality, it has been very difficult to study the role of DNA methylation in brain development. We have used cre-lox technology to generate forebrain-specific deletion of DNA methyltransferase 1 (Dnmt1), the enzyme required for the maintenance of DNA methylation. We find that demethylation of neurons in the cerebral cortex results in the failure of development of somatosensory barrel cortex. We also find that in spite of functional thalamocortical neurotransmission, thalamocortical long-term potentiation cannot be induced in slices from Dnmt1 conditional mutants. These studies emphasize the importance of DNA methylation for the development of sensory maps and suggest epigenetic mechanisms may play a role in the development of synaptic plasticity.

This study examines the temporal properties of geniculocortical and corticogeniculate (CG) pathways that link the lateral geniculate nucleus (LGN) and primary visual cortex in the ferret. Using electrical stimulation in the LGN to evoke action potentials in geniculocortical and CG axons, results show that conduction latencies are significantly faster in geniculocortical neurons than in CG neurons. Within each pathway, axonal latency and visual physiology support the view of sub-classes of neurons. By examining the timing of visual responses and the latency of CG feedback, estimates indicate that visual information can reach the cortex and return to the LGN as early as 60 msec following the onset of a visual stimulus. These findings place constraints on the functional role of corticogeniculate feedback for visual processing.

Mechanisms underlying seizure cessation remain elusive. The Lennox-Gastaut syndrome, a severe childhood epileptic disorder, is characterized by episodes of seizure with alternating epochs of spike-wave and fast run discharges. In a detailed computational model that incorporates extracellular potassium dynamics, we studied the dynamics of these state transitions between slow and fast oscillations. We show that dynamic modulation of synaptic transmission can cause termination of paroxysmal activity. An activity-dependent shift in the balance between synaptic excitation and inhibition towards more excitation caused seizure termination by favoring the slow oscillatory state, which permits recovery of baseline extracellular potassium concentration. We found that slow synaptic depression and change in chloride reversal potential can have similar effects on the seizure dynamics. Our results indicate a novel role for synaptic dynamics during epileptic neural activity patterns.

Thalamic relay neurons have homogeneous, adult-like firing properties and similar morphology by 12 days postnatally (PN 12). Parafascicular (Pf) neurons have a different morphology compared with typical thalamic relay neurons, but the development of their electrophysiological properties is not well studied. Intracellular recordings in PN 12-50 Pf neurons revealed several heterogeneous firing patterns different from those in thalamic relay neurons. Two types of cells were identified: Type I cells displayed a fast afterhyperpolarization (AHP) followed by a large-amplitude, slow AHP; whereas Type II cells had only a fast AHP. These cell types had overlapping membrane properties but differences in excitability. Some properties of Pf neurons were adult-like by PN 12, but, unlike thalamic relay neurons, there were significant maturational changes thereafter, including decreased action potential (AP) duration, increased fast AHP amplitude and increased excitability. Pf neurons did not exhibit rhythmic bursting and generally lacked low-threshold spike (LTS) responses that characterize thalamic relay neurons. Pf neurons exhibited nonlinear I-V relationships, and only a third of the cells expressed the time and voltage-dependent hyperpolarization activated (Ih) current, which declined with age. These results indicate that the morphological differences between Pf neurons and typical thalamic relay neurons are paralleled by electrophysiological differences, and that Pf membrane properties change during postnatal development.