Zoltan Nadasdy

Gamma (40-100 Hz) oscillation in the hippocampus of the behaving rat

The cellular generation and spatial distribution of gamma frequency (40– 100 Hz) activity was examined in the hippocampus of the awake rat. Field potentials and unit activity were recorded by multiple site silicon probes (5- and 16-site shanks) and wire electrode arrays. Gamma waves were highly coherent along the long axis of the dentate hilus, but average coherence decreased rapidly in the CA3 and CA1 directions. Analysis of short epochs revealed large fluctuations in coherence values between the dentate and CA1 gamma waves. Current source density analysis revealed large sinks and sources in the dentate gyrus with spatial distribution similar to the dipoles evoked by stimulation of the perforant path. The frequency changes of gamma and theta waves positively correlated (40–100 Hz and 5–10 Hz, respectively). Putative interneurons in the dentate gyrus discharged at gamma frequency and were phase-locked to the ascending part of the gamma waves recorded from the hilus. Following bilateral lesion of the entorhinal cortex the power and frequency of hilar gamma activity significantly decreased or disappeared. Instead, a large amplitude but slower gamma pattern (25–50 Hz) emerged in the CA3-CA1 network. We suggest that gamma oscillation emerges from an interaction between intrinsic oscillatory properties of interneurons and the network properties of the dentate gyrus. We also hypothesize that under physiological conditions the hilar gamma oscillation may be entrained by the entorhinal rhythm and that gamma oscillation in the CA3-CA1 circuitry is suppressed by either the hilar region or the entorhinal cortex.

Unsupervised spike detection and sorting with wavelets and superparamagnetic clustering

This study introduces a new method for detecting and sorting spikes from multiunit recordings. The method combines the wave let transform, which localizes distinctive spike features, with super paramagnetic clustering, which allows automatic classification of the data without assumptions such as low variance or gaussian distributions. Moreover, an improved method for setting amplitude thresholds for spike detection is proposed. We describe several criteria for implementation that render the algorithm unsupervised and fast. The algorithm is compared to other conventional methods using several simulated data sets whose characteristics closely resemble those of in vivo recordings. For these data sets, we found that the proposed algorithm outperformed conventional methods.

The basal forebrain corticopetal system revisited

ABSTRACT: The medial septum, diagonal bands, ventral pallidum, substantia innominata, globus pallidus, and internal capsule contain a heterogeneous population of neurons, including cholinergic and noncholinergic (mostly GABA containing), corticopetal projection neurons, and interneurons. This highly complex brain region, which constitutes a significant part of the basal forebrain has been implicated in attention, motivation, learning, as well as in a number of neuropsychiatric disorders, such as Alzheimers disease, Parkinsons disease, and schizophrenia. Part of the difficulty in understanding the functions of the basal forebrain, as well as the aberrant information‐processing characteristics of these disease states lies in the fact that the organizational principles of this brain area remained largely elusive. On the basis of new anatomical data, it is proposed that a large part of the basal forebrain corticopetal system be organized into longitudinal bands. Considering the topographic organization of cortical afferents to different divisions of the prefrontal cortex and a similar topographic projection of these prefrontal areas to basal forebrain regions, it is suggested that several functionally segregated cortico‐prefronto‐basal forebrain‐cortical circuits exist. It is envisaged that such specific “triangular” circuits could amplify selective attentional processing in posterior sensory cortical areas.

Neurons in the Basal Forebrain Project to the Cortex in a Complex Topographic Organization that Reflects Corticocortical Connectivity Patterns: An Experimental Study Based on Retrograde Tracing and 3D Reconstruction

The most prominent feature of the Basal Forebrain (BF) is the collection of large cortically projecting neurons (basal nucleus of Meynert) that serve as the primary source of cholinergic input to the entire cortical mantle. Despite its broad involvement in cortical activation, attention, and memory, the functional details of the BF are not well understood due to the anatomical complexity of the region. This study tested the hypothesis that basalocortical connections reflect cortical connectivity patterns. Distinct retrograde tracers were deposited into various frontal and posterior cortical areas, and retrogradely labeled cholinergic and noncholinergic neurons were mapped in the BF. Concurrently, we mapped retrogradely labeled cells in posterior cortical areas that project to various frontal areas, and all cell populations were combined in the same coordinate system. Our studies suggest that the cholinergic and noncholinergic projections to the neocortex are not diffuse, but instead, are organized into segregated or overlapping pools of projection neurons. The extent of overlap between BF populations projecting to the cortex depends on the degree of connectivity between the cortical targets of these projection populations. We suggest that the organization of projections from the BF may enable parallel modulation of multiple groupings of interconnected yet nonadjacent cortical areas.

Oscillatory and Intermittent Synchrony in the Hippocampus: Relevance to Memory Trace Formation

The different cell populations of the hippocampus are involved in behaviorregulated intermittent population bursts (sharp-waves, (SPW) and dentate spikes) and oscillations (theta, gamma and 200 Hz). SPW occur during consummatory behaviors and slow wave sleep. This field potential reflects summated EPSPs in the apical dendrites of CA1 pyramidal neurons as a result of population synchrony in the CA3 recurrent network. During SPW bursts, CA1 pyramidal cells display highly coherent transient network oscillations (200 Hz). Participating pyramidal cells discharge at a significantly lower rate than the frequency of the population oscillation and their action potentials are phase-locked to the simultaneously recorded oscillatory field potentials. Antagonistic to these intermittent events are the theta (6–10 Hz) and associated gamma (40–100 Hz) oscillations during exploratory behavior and REM sleep. In the intact rat the gamma pattern has its largest amplitude in the hilus, is modulated by theta and is entrained by the entorhinal input. The theta pattern is generated by several spatially distinct but highly coherent dipoles and requires an external pacemaker (septum).

Three-dimensional chemoarchitecture of the basal forebrain: Spatially specific association of cholinergic and calcium binding protein-containing neurons

The basal forebrain refers to heterogeneous structures located close to the medial and ventral surfaces of the cerebral hemispheres. It contains diverse populations of neurons, including the cholinergic cortically projecting cells that show severe loss in Alzheimers and related neurodegenerative diseases. The basal forebrain does not display any cytoarchitectural or other structural features that make it easy to demarcate functional boundaries, a problem that allowed different investigators to propose different organizational schemes. The present paper uses novel three-dimensional reconstructions and numerical analyses for studying the spatial organization of four major basal forebrain cell populations, the cholinergic, parvalbumin, calbindin and calretinin containing neurons in the rat. Our analyses suggest that the distribution of these four cell populations is not random but displays a general pattern of association. Within the cholinergic space (i.e. the volume occupied by the cortically projecting cholinergic cell bodies) the three other cell types form twisted bands along the longitudinal axis of a central dense core of cholinergic cells traversing the traditionally defined basal forebrain regions, (i.e. the medial septum, diagonal bands, the substantia innominata, pallidal regions and the bed nucleus of the stria terminalis). At a smaller scale, the different cell types within the cholinergic space occupy overlapping high-density cell clusters that are either chemically uniform or mixed. However, the cell composition of these high-density clusters is regionally specific. The proposed scheme of basal forebrain organization, using cell density or density relations as criteria, offers a new perspective on structure-function relationship, unconstrained by traditional region boundaries.

Information encoding and reconstruction from the phase of action potentials

Fundamental questions in neural coding are how neurons encode, transfer, and reconstruct information from the pattern of action potentials (APs) exchanged between different brain structures. We propose a general model of neural coding where neurons encode information by the phase of their APs relative to their subthreshold membrane oscillations. We demonstrate by means of simulations that AP phase retains the spatial and temporal content of the input under the assumption that the membrane potential oscillations are coherent across neurons and between structures and have a constant spatial phase gradient. The model explains many unresolved physiological observations and makes a number of concrete, testable predictions about the relationship between APs, local field potentials, and subthreshold membrane oscillations, and provides an estimate of the spatio-temporal precision of neuronal information processing.

Computational Anatomical Analysis of the Basal Forebrain Corticopetal System

The basal forebrain (BF) is comprised of a neurochemically heterogeneous population of neurons, including cholinergic, GABA-ergic, peptidergic, and possibly glutamatergic neurons, that project to the cerebral cortex, thalamus, amygdala, posterior hypothalamus and brain stem. This multitude of ascending and descending pathways participate in a similarly bewildering number of functions, including cognition, motivation, emotion, and autonomic regulation. Traditional anatomical methods failed to grasp the basic organizational principles of this brain area and likened it at best to the organization of the brain stem reticular formation. Our studies, using various computational methods for analyzing the spatial distribution and numerical relations of different chemically and hodologically characterized neuronal populations, as well as fully reconstructed electrophysiologically identified single neurons, began to unravel the organizational principles of the BF. According to our model, the different cell types form large-scale cell sheets that are aligned to each other in a specific manner Within each cell system, the neurons display characteristic discontinuous distributions, including high density clusters. As a result of nonhomogeneity within individual cell populations and partial overlapping between different cell types, the space containing the bulk of cholinergic neurons comprises a mosaic of various size cell clusters. The composition, dendritic orientation, and input—output relationships of these high density cell clusters show regional differences. It is proposed that these clusters represent specific sites (modules) where information processed in separate streams can be integrated. Via this BF mechanism a topographically organized prefrontal input could allocate attentional resources to cortical associational areas in a selective self-regulatory fashion.

Ultra-slow oscillations in cortical networks in vitro.

An ultra-slow oscillation (<0.01 Hz) in the network-wide activity of dissociated cortical networks is described in this article. This slow rhythm is characterized by the recurrence of clusters of large synchronized bursts of activity lasting approximately 1-3 min, separated by an almost equivalent interval of relatively smaller bursts. Such rhythmic activity was detected in cultures starting from the fourth week in vitro. Our analysis revealed that the propagation motifs of constituent bursts were strongly conserved across multiple oscillation cycles, and these motifs were more consistent at the electrode level compared with the neuronal level.

Visualization of density relations in large-scale neural networks.

The topological organization of interfacing neuronal populations in the basal forebrain of rats was investigated in 3D by using computational methods for extracting information about the spatial distribution of cell densities and density relations. We claim that numerical and spatial constraints imposed by these methods may help to define neuronal clusters in this brain area where simple two-dimensional histology failed to reveal such an arrangement. Neuronal clusters have been suggested in many brain regions as sites of integrative operations. Taking advantage of computerized data acquisition methods in the 3D reconstruction of large cell populations we introduced four basic methods to visualize density relations on simple and combined cell markers: Differential Density 3D Scatter Plot, Iso-relational Scatter plot, Iso-density Surface Rendering and Iso-relational Surface Rendering. These methods are described and exemplified on a 3D neuronal database acquired from mapping different chemically or hodologically defined cell populations in serial sections of the rat basal forebrain.