Short-term Synaptic Depression in the Feedforward Inhibitory Circuit in the Dorsal Lateral Geniculate Nucleus.

Synaptic short-term plasticity (STP) regulates synaptic transmission in an activity-dependent manner and thereby has important roles in the signal processing in the brain. In some synapses, a presynaptic train of action potentials elicits post-synaptic potentials that gradually increase during the train (facilitation), but in other synapses, these potentials gradually decrease (depression). We studied STP in neurons in the visual thalamic relay, the dorsal lateral geniculate nucleus (dLGN).

Functions of synapsins in corticothalamic facilitation: important roles of synapsin I.

Key Points: The synaptic vesicle associated proteins synapsin I and synapsin II have important functions in synaptic short-term plasticity. We investigated their functions in cortical facilitatory feedback to neurons in dorsal lateral geniculate nucleus (dLGN), feedback that has important functions in state-dependent regulation of thalamic transmission of visual input to cortex. We compared results from normal wild-type (WT) mice and synapsin knockout (KO) mice in several types of synaptic plasticity, and found clear differences between the responses of neurons in the synapsin I KO and the WT, but no significant differences between the synapsin II KO and the WT.

NMDA spike/plateau potentials in dendrites of thalamocortical neurons.

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.

Sensitive and critical periods in the development of handling induced seizures in mice lacking synapsins: differences between synapsin I and synapsin II knockouts.

Mice lacking either synapsin I or synapsin II develop handling induced seizures from around two months of age. In mice lacking synapsin I (synapsin 1 knock-out mice, Syn1KO mice) such seizures can either consist of mild myoclonic jerks or of fully developed generalized tonic-clonic seizures, and the two seizure types are quite evenly distributed. In mice lacking synapsin II (synapsin 2 knock-out mice, Syn2KO mice) all seizures are in the form of generalized tonic-clonic seizures.

Temporally advanced dynamic change of receptive field of lateral geniculate neurons during brief visual stimulation: Effects of brainstem peribrachial stimulation.

Processing of visual information in the brain seems to proceed from initial fast but coarse to subsequent detailed processing. Such coarse-to-fine changes appear also in the response of single neurons in the visual pathway. In the dorsal lateral geniculate nucleus (dLGN), there is a dynamic change in the receptive field (RF) properties of neurons during visual stimulation.

Terminals of the major thalamic input to visual cortex are devoid of synapsin proteins.

Synapsins are nerve-terminal proteins that are linked to synaptic transmission and key factors in several forms of synaptic plasticity. While synapsins are generally assumed to be ubiquitous in synaptic terminals, whether they are excluded from certain types of terminals is of interest. In the visual pathway, synapsins are lacking in photoreceptor and bipolar cell terminals as well as in retinogeniculate synapses.

Neuroethologically delineated differences in the seizure behavior of synapsin 1 and synapsin 2 knock-out mice.

The highly homologous nerve terminal phosphoproteins synapsin I and synapsin II have been linked to the pathogenesis of epilepsy through associations between synapsin gene mutations and epileptic disease in humans and to the observation of handling induced seizures in mice genetically depleted of one or both of these proteins. Whereas seizure behavior in mice lacking both synapsin I and synapsin II is well characterized, the seizure behavior in mice lacking either is less well studied. Through so called neuroethologically based analyses of fully established seizure behavior in Synapsin 1 and 2 knock-out mice (Syn1KO and Syn2KO mice) aged 4 1/2 months, this study reveals significant differences in the seizure behavior of the two genotypes: whereas Syn1KO mice show both partial and generalized forebrain seizure activity, Syn2KO mice show only fully generalized forebrain seizures.

A multi-compartment model for interneurons in the dorsal lateral geniculate nucleus.

GABAergic interneurons (INs) in the dorsal lateral geniculate nucleus (dLGN) shape the information flow from retina to cortex, presumably by controlling the number of visually evoked spikes in geniculate thalamocortical (TC) neurons, and refining their receptive field. The INs exhibit a rich variety of firing patterns: Depolarizing current injections to the soma may induce tonic firing, periodic bursting or an initial burst followed by tonic spiking, sometimes with prominent spike-time adaptation. When released from hyperpolarization, some INs elicit rebound bursts, while others return more passively to the resting potential.

Coarse-to-fine changes of receptive fields in lateral geniculate nucleus have a transient and a sustained component that depend on distinct mechanisms.

Visual processing in the brain seems to provide fast but coarse information before information about fine details. Such dynamics occur also in single neurons at several levels of the visual system. In the dorsal lateral geniculate nucleus (LGN), neurons have a receptive field (RF) with antagonistic center-surround organization, and temporal changes in center-surround organization are generally assumed to be due to a time-lag of the surround activity relative to center activity.

Cortical feedback regulation of input to visual cortex: role of intrageniculate interneurons.

Neurons in the dorsal lateral geniculate nucleus (dLGN) process and transmit visual signals from retina to visual cortex. The processing is dynamically regulated by cortical excitatory feedback to neurons in dLGN, and synaptic short-term plasticity (STP) has an important role in this regulation. It is known that corticogeniculate synapses on thalamocortical (TC) projection-neurons are facilitating, but type and characteristics of STP of synapses on inhibitory interneurons in dLGN are unknown.

Electroencephalographic characterization of seizure activity in the synapsin I/II double knockout mouse.

We present a detailed comparison of the behavioral and electrophysiological development of seizure activity in mice genetically depleted of synapsin I and synapsin II (SynDKO mice), based on combined video and surface EEG recordings. SynDKO mice develop handling-induced epileptic seizures at the age of 2months. The seizures show a very regular behavioral pattern, where activity is initially dominated by truncal muscle contractions followed by various myoclonic elements.

Seizure logging: A new approach to synchronized cable-free EEG and video recordings of seizure activity in mice.

We describe a new cable-free, non-telemetric method for synchronized electrophysiological and video recordings of seizure activity in freely moving mice. The electrophysiological recordings were made by a head-mounted 4-channel data-logging device, allowing the mouse to move freely in its cage, and even to be moved from cage to cage under ongoing recording. Seizures were studied in Synapsin I/II double knock-out (SynDKO) mice, a genetically engineered mouse line that shows seizures upon daily handling procedures such as tail lifting during cage changes, much in resemblance to the more studied El mouse.

Activity patterns govern synapse-specific AMPA receptor trafficking between deliverable and synaptic pools.

In single neurons, glutamatergic synapses receiving distinct afferent inputs may contain AMPA receptors (-Rs) with unique subunit compositions. However, the cellular mechanisms by which differential receptor transport achieves this synaptic diversity remain poorly understood. In lateral geniculate neurons, we show that retinogeniculate and corticogeniculate synapses have distinct AMPA-R subunit compositions.

Seizure elements and seizure element transitions during tonic-clonic seizure activity in the synapsin I/II double knockout mouse: a neuroethological description.

Inactivation of genes for the synaptic terminal proteins synapsin I and synapsin II leads to development of epileptic seizures in mice (Syn-DKO mice) in which no other behavioral abnormalities or any gross anatomical brain deformities have been reported. In humans, mutated synapsin I is associated with epilepsy. Thus, the Syn-DKO mouse might model human seizure development.

Changes in firing pattern of lateral geniculate neurons caused by membrane potential dependent modulation of retinal input through NMDA receptors.

An optimal visual stimulus flashed on the receptive field of a retinal ganglion cell typically evokes a strong transient response followed by weaker sustained firing. Thalamocortical (TC) neurons in the dorsal lateral geniculate nucleus, which receive their sensory input from retina, respond similarly except that the gain, in particular of the sustained component, changes with level of arousal. Several lines of evidence suggest that retinal input to TC neurons through NMDA receptors plays a key role in generation of the sustained response, but the mechanisms for the state-dependent variation in this component are unclear.

Dynamics of spatial resolution of single units in the lateral geniculate nucleus of cat during brief visual stimulation.

Sharpness of vision depends on the resolution of details conveyed by individual neurons in the visual pathway. In the dorsal lateral geniculate nucleus (LGN), the neurons have receptive fields with center-surround organization, and spatial resolution may be measured as the inverse of center size. We studied dynamics of receptive field center size of single LGN neurons during the response to briefly (400-500 ms) presented static light or dark spots.

Synapsin utilization differs among functional classes of synapses on thalamocortical cells.

Several proteins in nerve terminals participate in synaptic transmission between neurons. The synapsins, which are synaptic vesicle-associated proteins, have widespread distribution in the brain and are assumed essential for sustained recruitment of vesicles during high rates of synaptic transmission. We compared the role of synapsins in two types of glutamatergic synapses on thalamocortical cells in the dorsal lateral geniculate nucleus of mice: retinogeniculate synapses, which transmit primary afferent input at high frequencies and show synaptic depression, and corticogeniculate synapses, which provide modulatory feedback at lower frequencies and show synaptic facilitation.

Postnatal development of GABAergic signalling in the rat lateral geniculate nucleus: presynaptic dendritic mechanisms.

Diverse forms of GABAergic inhibition are found in the mature brain. To understand how this diversity develops, we studied the changes in morphology of inhibitory interneurons and changes in interneuron-mediated synaptic transmission in the rat dorsal lateral geniculate nucleus (dLGN). We found a steady expansion of the dendritic tree of interneurons over the first three postnatal weeks.

Brainstem modulation of visual response properties of single cells in the dorsal lateral geniculate nucleus of cat.

The dorsal lateral geniculate nucleus (dLGN) transmits visual signals from the retina to the cortex. In the dLGN the antagonism between the centre and the surround of the receptive fields is increased through intrageniculate inhibitory mechanisms. Furthermore, the transmission of signals through the dLGN is modulated in a state-dependent manner by input from various brainstem nuclei including an area in the parabrachial region (PBR) containing cholinergic cells involved in the regulation of arousal and sleep.

AMPA and NMDA currents show different short-term depression in the dorsal lateral geniculate nucleus of the rat.

Paired-pulse depression was studied at the glutamatergic synapse between retinal afferents and thalamocortical cells in the rat dorsal lateral geniculate nucleus. The main objective of this study was to examine the contributions of the pre- and postsynaptic sites to this depression by comparing AMPA- and NMDA-receptor-mediated responses. Equal depression of the two receptor components would indicate involvement of presynaptic mechanisms, while differences in depression would indicate involvement of postsynaptic mechanisms.

AMPA receptor properties at the synapse between retinal afferents and thalamocortical cells in the dorsal lateral geniculate nucleus of the rat.

The thalamocortical (TC) cells in dorsal lateral geniculate nucleus transfer signals from retinal afferents to the primary visual cortex. The excitatory retinal input to the TC cells is mediated by ionotropic receptors of the N-methyl-D-aspartate (NMDA) and non-NMDA type. In the present study the excitatory postsynaptic current (EPSC) mediated by non-NMDA receptors in this synapse was characterised by means of voltage-clamp recordings from TC neurons in rat thalamic slices.

Mathematical models for the spatial receptive-field organization of nonlagged X-cells in dorsal lateral geniculate nucleus of cat.

Spatial receptive fields of relay cells in dorsal lateral geniculate nucleus (dLGN) have commonly been modeled as a difference of two Gaussian functions. We present alternative models for dLGN cells which take known physiological couplings between retina and dLGN and within dLGN into account. The models include excitatory input from a single retinal ganglion cell and feedforward inhibition via intrageniculate interneurons.

Spatial summation and center-surround antagonism in the receptive field of single units in the dorsal lateral geniculate nucleus of cat: comparison with retinal input.

Spatial summation and degree of center-surround antagonism were examined in the receptive field of nonlagged cells in the dorsal lateral geniculate nucleus (dLGN). We recorded responses to stationary light or dark circular spots that were stepwise varied in width. The spots were centered on the receptive field.

Muscarinic regulation of dendritic and axonal outputs of rat thalamic interneurons: a new cellular mechanism for uncoupling distal dendrites.

Inhibition is crucial for sharpening the sensory information relayed through the thalamus. To understand how the interneuron-mediated inhibition in the thalamus is regulated, we studied the muscarinic effects on interneurons in the lateral posterior nucleus and lateral geniculate nucleus of the thalamus. Here, we report that activation of muscarinic receptors switched the firing pattern in thalamic interneurons from bursting to tonic.

Roles of N-methyl-D-aspartate receptors in ocular dominance plasticity in developing visual cortex: re-evaluation.

We have re-examined whether N-methyl-D-aspartate receptors play a specific role in experience-dependent plasticity in kitten visual cortex. A specific antagonist of this glutamate receptor subtype, D,L-2-amino-5-phosphonovaleric acid, was directly and continuously infused into kitten striate cortex for one week concurrently with monocular lid suture. In the hemisphere infused with 50 mM antagonist, we found the usual shift in ocular dominance toward the open eye with only a few binocular cells remaining.