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ABSTRACT: Diverse sources of GABAergic inhibition are a major feature of cortical networks, but distinct inhibitory input systems have not been systematically characterized in the thalamus. Here, we contrasted the properties of two independent GABAergic pathways in the posterior thalamic nucleus of rat, one input from the reticular thalamic nucleus (nRT), and one "extrareticular" input from the anterior pretectal nucleus (APT). The vast majority of nRT-thalamic terminals formed single synapses per postsynaptic target and innervated thin distal dendrites of relay cells. In contrast, single APT-thalamic terminals formed synaptic contacts exclusively via multiple, closely spaced synapses on thick relay cell dendrites. Quantal analysis demonstrated that the two inputs displayed comparable quantal amplitudes, release probabilities, and multiple release sites. The morphological and physiological data together indicated multiple, single-site contacts for nRT and multisite contacts for APT axons. The contrasting synaptic arrangements of the two pathways were paralleled by different short-term plasticities. The multisite APT-thalamic pathway showed larger charge transfer during 50-100 Hz stimulation compared with the nRT pathway and a greater persistent inhibition accruing during stimulation trains. Our results demonstrate that the two inhibitory systems are morpho-functionally distinct and suggest and that multisite GABAergic terminals are tailored for maintained synaptic inhibition even at high presynaptic firing rates. These data explain the efficacy of extrareticular inhibition in timing relay cell activity in sensory and motor thalamic nuclei. Finally, based on the classic nomenclature and the difference between reticular and extrareticular terminals, we define a novel, multisite GABAergic terminal type (F3) in the thalamus.
Journal of Neuroscience 12/2008; 28(46):11848-61. · 7.11 Impact Factor
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ABSTRACT: The rodent somatosensory cortex contains barrel-related and septa-related circuits representing two separate streams of vibrissa information processing that differ in their response patterns and anatomical connections. Whereas barrel-related circuits process lemniscal inputs that transit through the thalamic barreloids, septa-related circuits process paralemniscal inputs and inputs that are relayed through the ventral lateral part of the ventral posterior medial nucleus (VPMvl). Septa-projecting thalamic afferents also target the secondary somatosensory cortical area. Although a number of studies have examined response properties in the lemniscal pathway, and demonstrated that barreloids receive feedback from specific sets of corticothalamic and reticular thalamic neurons, such information is currently lacking for the VPMvl. In the present study, we show that in sharp contrast to the relay cells of the barreloids VPMvl neurons exhibit large multiwhisker receptive fields that are independent of input from the principal trigeminal nucleus. Results also suggest that the topography of receptive fields and response properties in VPMvl rely on converging input from neurons of the interpolaris trigeminal nucleus. Tracer injection and single-cell labeling further reveal that the VPMvl receives input from specific populations of reticular thalamic and corticothalamic neurons. Together, these results confirm the status of the VPMvl as a thalamic relay of an independent parallel pathway of vibrissa information processing. They further indicate that a sensory pathway does not merely consist on a three-neuron chain that links the vibrissae to the cerebral cortex, but that it also involves specific sets of topographically related corticothalamic and reticular thalamic projections.
Journal of Neuroscience 06/2008; 28(20):5169-77. · 7.11 Impact Factor
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ABSTRACT: The anterior pretectal nucleus (APT) and the zona incerta (ZI) are diencephalic nuclei that exert a strong inhibitory influence selectively in higher order thalamic relays. The APT is also known to project to the ZI as well as the thalamus, but anatomical details of the APT-ZI projection have not been described. In the present study, the efferent pathways of the APT were examined in the APT-ZI-thalamus network by using anterograde and retrograde tracing in combination with pre- and postembedding immunocytochemical stainings and in situ hybridization. The vast majority of APT fibers selectively innervated the parvalbumin-positive, ventral part of the ZI, which contains ZI neurons with axons projecting to higher order thalamic nuclei. The APT-ZI pathway consisted of both gamma-aminobutyric acid (GABA)-negative and GABA-positive components; 38.2% of the terminals in the ZI contained GABA, and 8.6% of the projecting somata in the APT were glutamic acid decarboxylase 67 (GAD67) mRNA positive. The combination of parvalbumin immunostaining with retrograde tracing showed that strongly and weakly parvalbumin-positive as well as parvalbumin-negative neurons were all among the population of APT cells projecting to the ZI. Similar heterogeneity was found among the APT cells projecting to the thalamus. Double retrograde tracing from higher order thalamic nuclei and their topographically matched ZI regions revealed hardly any APT neuron with dual projections. Our data suggest that both ZI and the higher order thalamic relays are innervated by distinct, physiologically heterogeneous APT neurons. These various efferent pathways probably interact via the rich recurrent collaterals of the projecting APT cells. Therefore, the powerful, GABAergic APT and ZI outputs to the thalamus are apparently co-modulated in a synergistic manner via dual excitatory and inhibitory APT-ZI connections.
The Journal of Comparative Neurology 02/2008; 506(1):122-40. · 3.81 Impact Factor
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ABSTRACT: The zona incerta (ZI) is at the crossroad of almost all major ascending and descending fiber tracts and targets numerous brain centers from the thalamus to the spinal cord. Effective ascending drive of ZI cells has been described, but the role of descending cortical signals in patterning ZI activity is unknown. Cortical control over ZI function was examined during slow cortical waves (1-3 Hz), paroxysmal high-voltage spindles (HVSs), and 5-9 Hz oscillations in anesthetized rats. In all conditions, rhythmic cortical activity significantly altered the firing pattern of ZI neurons recorded extracellularly and labeled with the juxtacellular method. During slow oscillations, the majority of ZI neurons became synchronized to the depth-negative phase ("up state") of the cortical waves to a degree comparable to thalamocortical neurons. During HVSs, ZI cells displayed highly rhythmic activity in tight synchrony with the cortical oscillations. ZI neurons responded to short epochs of cortical 5-9 Hz oscillations, with a change in the interspike interval distribution and with an increase in spectral density in the 5-9 Hz band as measured by wavelet analysis. Morphological reconstruction revealed that most ZI cells have mediolaterally extensive dendritic trees and very long dendritic segments. Cortical terminals established asymmetrical synapses on ZI cells with very long active zones. These data suggest efficient integration of widespread cortical signals by single ZI neurons and strong cortical drive. We propose that the efferent GABAergic signal of ZI neurons patterned by the cortical activity can play a critical role in synchronizing thalamocortical and brainstem rhythms.
Journal of Neuroscience 03/2007; 27(7):1670-81. · 7.11 Impact Factor
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ABSTRACT: Sensory stimuli evoke strong responses in thalamic relay cells, which ensure a faithful relay of information to the neocortex. However, relay cells of the posterior thalamic nuclear group in rodents, despite receiving significant trigeminal input, respond poorly to vibrissa deflection. Here we show that sensory transmission in this nucleus is impeded by fast feedforward inhibition mediated by GABAergic neurons of the zona incerta. Intracellular recordings of posterior group neurons revealed that the first synaptic event after whisker deflection is a prominent inhibition. Whisker-evoked EPSPs with fast rise time and longer onset latency are unveiled only after lesioning the zona incerta. Excitation survives barrel cortex lesion, demonstrating its peripheral origin. Electron microscopic data confirm that trigeminal axons make large synaptic terminals on the proximal dendrites of posterior group cells and on the somata of incertal neurons. Thus, the connectivity of the system allows an unusual situation in which inhibition precedes ascending excitation resulting in efficient shunting of the responses. The dominance of inhibition over excitation strongly suggests that the paralemniscal pathway is not designed to relay inputs triggered by passive whisker deflection. Instead, we propose that this pathway operates through disinhibition, and that the posterior group forwards to the cerebral cortex sensory information that is contingent on motor instructions.
Journal of Neuroscience 09/2005; 25(33):7489-98. · 7.11 Impact Factor
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ABSTRACT: GABAergic signaling is central to the function of the thalamus and has been traditionally attributed primarily to the nucleus reticularis thalami (nRT). Here we present a GABAergic pathway, distinct from the nRT, that exerts a powerful inhibitory effect selectively in higher-order thalamic relays of the rat. Axons originating in the anterior pretectal nucleus (APT) innervated the proximal dendrites of relay cells via large GABAergic terminals with multiple release sites. Stimulation of the APT in an in vitro slice preparation revealed a GABA(A) receptor-mediated, monosynaptic IPSC in relay cells. Activation of presumed single APT fibers induced rebound burst firing in relay cells. Different APT neurons recorded in vivo displayed fast bursting, tonic, or rhythmic firing. Our data suggest that selective extrareticular GABAergic control of relay cell activity will result in effective, state-dependent gating of thalamocortical information transfer in higher-order but not in first-order relays.
Neuron 04/2005; 45(6):929-40. · 14.74 Impact Factor
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ABSTRACT: Little is known about the neurochemical features of the nucleus reuniens thalami (RE). In the present study, immunocytochemical experiments were performed to characterize the expression pattern of certain neurochemical markers, e.g. the calcium-binding proteins calbindin and calretinin and several neuropeptides. Colocalization studies revealed that half of the calbindin-positive cells express calretinin, and numerous calretinin-immunoreactive neurons contain calbindin. In contrast, immunolabelling for neuropeptides did not reveal cell bodies in the RE. The RE establishes widespread connections with several limbic structures. To correlate these projection patterns with the neurochemical characteristics of RE neurons, the retrograde tracer [3H]D-aspartate, which is selectively taken up by high affinity uptake sites that use glutamate as neurotransmitter, and the nonselective retrograde tracer wheatgerm agglutinin-conjugated colloidal gold was injected into the stratum lacunosum moleculare of the hippocampal CA1 subfield and into the medial septum. The results provide direct anatomical demonstration of aspartatergic/glutamatergic projection from the RE to the hippocampus and to the medial septum. Nearly all of the projecting neurons proved to be calbindin-immunopositive and many of them expressed calretinin. Both retrograde labelling techniques revealed that neurons projecting to the hippocampus were located in clusters in the dorsolateral part of the RE, whereas neurons projecting to the medial septum were mainly distributed in the ventromedial portion of the nucleus, indicating that different cell populations project to these limbic areas. These results suggest that neurons in the RE are heterogeneous and contribute to the excitatory innervation of the septo-hippocampal system.
European Journal of Neuroscience 11/2002; 16(7):1227-39. · 3.63 Impact Factor
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ABSTRACT: Az OTKA pályázat során leírtunk és karakterizáltunk egy új gátlás-típust a talamuszban. E gátlórendszer axonvégződései és az általuk közvetített gátlás különbözött a talamuszban jól ismert gátlórendszerek tulajdonságaitól. Az axonterminálisok ultrastruktúrája és az általuk beidegzett célelemek hatékony gátlásra utaltak. Élettani kísérletek igazolták az anatómiai predikciókat és kimutatták, hogy ez a gátlás típus hatékony információ átvitelre képes magas frekvenciás impulzusok esetén is, mikor az ismert gátlópálya hatékonysága jelentősen csökken. Az új gátlás-típus képes megakadályozni a beidegzett talamikus sejtek működését, illetve képes kiváltani a karaterisztikus visszacsapó választ. Az új gátlás-típust sikerült azonosítani több pálya esetén, köztük főemlősökben a Parkinson-kórban érintett talamikus bemenetek esetében is. A pályázat során részletesen vizsgáltuk az új gátló pálya eredő sejtjeinek szerkezetét és működését. Egy új gátlópálya leírása, melyet egyedi működési mechanizmusok jellemeznek felveti a lehetőségét e pálya szelektív modulációjának. Olyan drogok, melyek ezen a speciális gátlóterminálison hatnak segíthetnek azon tünetek enyhítésén, melyeket e pályák aberráns aktivitása okoz (pl. Parkinson-kór, krónikus fájdalom). | During the OTKA project we discovered and characterized a novel inhibitory element in the thalamus. The structure of the nerve endings, their mode of action and the activity of the nerve cells were all different from the previously described inhibitory pathways in this brain centre. The anatomy of the nerve terminals and the nerve elements they contacted indicated powerful inhibitory action. Physiological measurements verified the anatomical predictions and demonstrated that these connections faithfully transfer inhibitory signals even at very high frequency, when the effectiveness of other inhibitory pathways is much reduced. We demonstrated that these inhibitory inputs are indeed able to silence thalamic neurons or induce strong, so-called, ?postinhibitory rebound? activity. The morhology and the actvity of the parent cells of these pathways has also been extensively characterized. We described several of these pathways in different thalamic nuclei most importantly in those known to be involved in Parkinson's disease. Discovering a separate class of inhibitory pathways in the thalamus with distinct mode of action raises the hope for their selective modulation. Drugs which acts on these terminals can help to alleviate the symptoms linked to the aberrant activity of these specialized inhibitory pathways.
