A tecto-thalamo-nucleus caudatus rendszer anatómiai, élettani és funkcionális vizsgálata házimacskában és makákó majomban = Analysis of the Tecto-Thalamo-Caudate Nucleus System in the feline and macaque brain: Anatomy, Physiology, Function, and Possible Evolutionary Significance

Morfológiai kísérleteinkben igazoltuk a tecto-thalamo-corticalis tengely (colliculus superior (CS)-nucleus suprageniculatus (Sg)-anterior ectosylvius kéreg (AES)) és a bazális ganglionok anatómiai kapcsolatát. A substantia nigra pars reticularisból (SNr) érkező afferensek a Sg-ban kapcsolódnak át a nucleus caudatus (NC) felé. Hasonló módon a Sg az átkapcsoló állomás a CS-ból érkező afferensek és az AES kéreg között. Igazoltuk továbbá az AES asszociációs kéregrészből a NC-hoz futó direkt vizuális pályát is. Az egysejt aktivitások és a mezőpotenciálok keresztkorrelációs analízise is a NC és a felszálló tectofugális vizuális rendszer szoros kapcsolatát mutatta, amiben döntő szerepe van a hátsó thalamus Sg magjának. A felszálló tectofugalis rendszer időbeli és térbeli vizuális tulajdonságainak vizsgálatával igazoltuk, hogy a CS-ban, a NC-ben, a Sg-ban és az AES kéregben levő neuronok hatékony időbeli és térbeli szűrőként működnek az alacsony térbeli és magas időbeli frekvenciadoménen belül. Megszerkesztettük továbbá a NC neuronok spatio-temporalis spectralis receptív mezőit és igazoltuk a térbeli vizuális információ megosztott populációs kódját a NC-ban. Eredményeink szerint a felszálló tectofugális rendszer és a vele szoros kapcsolatban levő bazális ganglionok közös szereppel bírnak a mozgások és a sebesség érzékelésében, aktivitásuk a mozgások során bekövetkező szenzoros változásokat is tükrözi, és így hozzájárulnak a szenzomotoros működések koordinálásához. | In our morphological experiments we established the existence of anatomical connections between the superior colliculus (CS)- suprageniculate nucleus (Sg)- anterior ectosylvian cortex (AES) tecto-thalamo-cortical axis and the basal ganglia. Afferentation from the reticular part of the substantia nigra (SNr) is relayed toward the caudate nucleus (CN) via Sg. Likewise, Sg is a relay for afferentation of CS origin toward AES. A direct visual pathway from AES to CN has also been described. A cross-correlation analysis of single unit activity and local field potentials revealed a strong connection between CN and the ascending tectofugal visual system, in which Sg plays a major role. Through the analysis of the temporal and spatial visual response characteristics we verified that neuron sin CS, CN, Sg and AES act as temporal and spatial filters in the low spatial and high temporal frequency domain. The spatio-temporal spectral receptive field of CN neurons has been determined and the existence of distributed population coding within CN has been established. Our results suggest that the ascending tectofugal system and the basal ganglia detect motion and speed in strong interconnection, and their activity also reflects sensory changes during motion, therefore, they jointly support the coordination of sensorimotor functions

The first synthesis of 3-deoxyoripavine and its utilization in the preparation of 10-deoxyaporphines and cyprodime

The synthesis of 3-deoxyoripavine (7) was realized as a novel and promising intermediate towards the synthesis of the important class of dopaminergic and/or serotonergic 10- deoxyaporphines and the special pharmacological tool µ opioid antagonist cyprodime. Generally, the preparation of these valuable biologically active compounds was achieved in remarkable yields

Role of Hippocampal CA2 Region in Triggering Sharp-Wave Ripples

Sharp-wave ripples (SPW-Rs) in the hippocampus are implied in memory consolidation, as shown by observational and interventional experiments. However, the mechanism of their generation remains unclear. Using two-dimensional silicon probe arrays, we investigated the propagation of SPW-Rs across the hippocampal CA1, CA2, and CA3 subregions. Synchronous activation of CA2 ensembles preceded SPW-R-related population activity in CA3 and CA1 regions. Deep CA2 neurons gradually increased their activity prior to ripples and were suppressed during the population bursts of CA3-CA1 neurons (ramping cells). Activity of superficial CA2 cells preceded the activity surge in CA3-CA1 (phasic cells). The trigger role of the CA2 region in SPW-R was more pronounced during waking than sleeping. These results point to the CA2 region as an initiation zone for SPW-Rs

Closed-loop control of epilepsy by transcranial electrical stimulation

Many neurological and psychiatric diseases are associated with clinically detectable, altered brain dynamics. The aberrant brain activity, in principle, can be restored through electrical stimulation. In epilepsies, abnormal patterns emerge intermittently, and therefore, a closed-loop feedback brain control that leaves other aspects of brain functions unaffected is desirable. Here, we demonstrate that seizure-triggered, feedback transcranial electrical stimulation (TES) can dramatically reduce spike-and-wave episodes in a rodent model of generalized epilepsy. Closed-loop TES can be an effective clinical tool to reduce pathological brain patterns in drug-resistant patients.Fil: Berényi, Antal. Rutgers University; Estados Unidos. University of New York; Estados Unidos. University of Szeged; HungríaFil: Belluscio, Mariano Andres. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Rutgers University; Estados UnidosFil: Mao, Dun. Rutgers University; Estados UnidosFil: Buzsáki, György. Rutgers University; Estados Unidos. University of New York; Estados Unido

Spatially distributed local fields in the hippocampus encode rat position

Although neuronal spikes can be readily detected from extracellular recordings, synaptic and subthreshold activity remains undifferentiated within the local field potential (LFP). In the hippocampus, neurons discharge selectively when the rat is at certain locations, while LFPs at single anatomical sites exhibit no such place-tuning. Nonetheless, because the representation of position is sparse and distributed, we hypothesized that spatial information can be recovered from multiple-site LFP recordings. Using high-density sampling of LFP and computational methods, we show that the spatiotemporal structure of the theta rhythm can encode position as robustly as neuronal spiking populations. Because our approach exploits the rhythmicity and sparse structure of neural activity, features found in many brain regions, it is useful as a general tool for discovering distributed LFP codes

Optogenetic activation of septal cholinergic neurons suppresses sharp wave ripples and enhances theta oscillations in the hippocampus

Theta oscillations in the limbic system depend on the integrity of the medial septum. The different populations of medial septal neurons (cholinergic and GABAergic) are assumed to affect different aspects of theta oscillations. Using optogenetic stimulation of cholinergic neurons in ChAT-Cre mice, we investigated their effects on hippocampal local field potentials in both anesthetized and behaving mice. Cholinergic stimulation completely blocked sharp wave ripples and strongly suppressed the power of both slow oscillations (0.5-2 Hz in anesthetized, 0.5-4 Hz in behaving animals) and supratheta (6-10 Hz in anesthetized, 10-25 Hz in behaving animals) bands. The same stimulation robustly increased both the power and coherence of theta oscillations (2-6 Hz) in urethane-anesthetized mice. In behaving mice, cholinergic stimulation was less effective in the theta (4-10 Hz) band yet it also increased the ratio of theta/slow oscillation and theta coherence. The effects on gamma oscillations largely mirrored those of theta. These findings show that medial septal cholinergic activation can both enhance theta rhythm and suppress peri-theta frequency bands, allowing theta oscillations to dominate

Theta Phase Segregation of Input-Specific Gamma Patterns in Entorhinal-Hippocampal Networks

Precisely how rhythms support neuronal communication remains obscure. We investigated interregional coordination of gamma oscillations using high-density electrophysiological recordings in the rat hippocampus and entorhinal cortex. We found that 30–80 Hz gamma dominated CA1 local field potentials (LFPs) on the descending phase of CA1 theta waves during navigation, with 60–120 Hz gamma at the theta peak. These signals corresponded to CA3 and entorhinal input, respectively. Above 50 Hz, interregional phase-synchronization of principal cell spikes occurred mostly for LFPs in the axonal target domain. CA1 pyramidal cells were phase-locked mainly to fast gamma (>100 Hz) LFP patterns restricted to CA1, which were strongest at the theta trough. While theta phase coordination of spiking across entorhinal-hippocampal regions depended on memory demands, LFP gamma patterns below 100 Hz in the hippocampus were consistently layer specific and largely reflected afferent activity. Gamma synchronization as a mechanism for interregional communication thus rapidly loses efficacy at higher frequencies

Local Generation and Propagation of Ripples along the Septotemporal Axis of the Hippocampus

A topographical relationship exists between the septotemporal segments of the hippocampus and their entorhinal–neocortical targets, but the physiological organization of activity along the septotemporal axis is poorly understood. We recorded sharp-wave ripple patterns in rats during sleep from the entire septotemporal axis of the CA1 pyramidal layer. Qualitatively similar ripples emerged at all levels. From the local seed, ripples traveled septally or temporally at a speed of ∼0.35 m/s, and the spatial spread depended on ripple magnitude. Ripples propagated smoothly across the septal and intermediate segments of the hippocampus, but ripples in the temporal segment often remained isolated. These findings show that ripples can combine information from the septal and intermediate hippocampus and transfer integrated signals downstream. In contrast, ripples that emerged in the temporal pole broadcast largely independent information to their cortical and subcortical targets

Higher-order thalamic nuclei facilitate the generalization and maintenance of spike-and-wave discharges of absence seizures

Spike-and-wave discharges (SWDs), generated by the cortico-thalamo-cortical (CTC) network, are pathological, large amplitude oscillations and the hallmark of absence seizures (ASs). SWDs begin in a cortical initiation network in both humans and animal models, including the Genetic Absence Epilepsy Rats from Strasbourg (GAERS), where it is located in the primary somatosensory cortex (S1). The behavioral manifestation of an AS occurs when SWDs spread from the cortical initiation site to the whole brain, however, the mechanisms behind this rapid propagation remain unclear. Here we investigated these processes beyond the principal CTC network, in higher-order (HO) thalamic nuclei (lateral posterior (LP) and posterior (PO) nuclei) since their diffuse connectivity and known facilitation of intracortical communications make these nuclei key candidates to support SWD generation and maintenance. In freely moving GAERS, multi-site LFP in LP, PO and multiple cortical regions revealed a novel feature of SWDs: during SWDs there are short periods (named SWD-breaks) when cortical regions far from S1, such the primary visual cortex (V1), become transiently unsynchronized from the ongoing EEG rhythm. Inactivation of HO nuclei with local muscimol injections or optogenetic perturbation of HO nuclei activity increased the occurrence of SWD-breaks and the former intervention also increased the SWD propagation-time from S1. The neural underpinnings of these findings were explored further by silicon probe recordings from single units of PO which uncovered two previously unknown groups of excitatory neurons based on their burst firing dynamics at SWD onset. Moreover, a switch from tonic to burst firing at SWD onset was shown to be an important feature since it was much less prominent for non-generalized events, i.e. SWDs that remained local to S1. Additionally, one group of neurons showed a reverse of this switch during SWD-breaks, demonstrating the importance of this firing pattern throughout the SWD. In summary, these results support the view that multiple HO thalamic nuclei are utilized at SWD onset and contribute to cortical synchrony throughout the paroxysmal discharge