Recurrence 1Electrical stimulation (ES) is used in animals and humans to study potential causal links between neural activity and specific cognitive functions. Recently, it has found increased application in electrotherapy and neural prostheses as well. However, how ES-elicited signals propagate in brain tissues is still unclear. Here we used combined electrostimulation, neurophysiology, microinjection and fMRI to study the cortical activity patterns elicited during stimulation of cortical afferents in monkeys. We find that stimulation of a site in LGN (lateral geniculate nucleus) increases the fMRI signal in the regions of primary visual cortex (V1) receiving input from that site, but suppresses it in the retinotopically matched regions of extrastriate cortex. In agreement with previous observations, intracranial recordings show that immediately after a stimulation pulse a long-lasting inhibition follows a short excitatory response. Following microinjections of GABA (γ-aminobutyric acid) antagonists in V1, LGN stimulation induces positive fMRI signals in all cortical areas. Taken together, our findings suggest that ES disrupts cortico-cortical signal propagation by silencing the output of any neocortical area whose afferents are electrically stimulated.We recently developed and optimized the esfMRI (combined ES and fMRI) methodology for experiments in anesthetized and behaving monkeys 1, 2 . Our first experiments, including fMRI-based estimations of tissue excitability (rheobase and chronaxie measurements), showed that electrical stimulation of the primary visual cortex V1 mainly excites large pyramidal cells and axons, eliciting positive BOLD responses (PBR) in topographically matched regions of extrastriate areas such as V2, V3, V3A, V4, and MT (V5); all monosynaptic targets of the primary visual cortex. These findings are consistent with the well-established anatomical connections between V1 and the extrastriate cortex of macaque monkeys 3 . One puzzling observation in our initial studies was the clear lack of transsynaptic effects during cortical stimulation. In the present study, we stimulated either the LGN or the pulvinar (Pul) in anesthetized and alert monkeys in order to systematically examine the propagation of ES-induced signals.We demonstrate that electrical stimulation of a thalamic site indeed suppresses the neural activity of its projection regions in visual cortex. The strong reduction in BOLD response is likely due to synaptic inhibition and it be can be reversed by injections of GABA antagonists in V1. In agreement with the fMRI results, intracortical recordings show that an electric pulse evokes an action potential followed by a pronounced and long-lasting inhibition. Such disruptive effects of cortical afferent stimulation on the activity of projection neurons have already been reported. Yet, by using the combined physiology, pharmacology and fMRI approach here we illustrate for the first time the extent and generality of ES-induced activity suppression, and we propose that many behavioral e...

Electrical microstimulation has been used to elucidate cortical function. This review discusses neuronal excitability and effective current spread estimated by using three different methods: 1) single-cell recording, 2) behavioral methods, and 3) functional magnetic resonance imaging (fMRI). The excitability properties of the stimulated elements in neocortex obtained using these methods were found to be comparable. These properties suggested that microstimulation activates the most excitable elements in cortex, that is, by and large the fibers of the pyramidal cells. Effective current spread within neocortex was found to be greater when measured with fMRI compared with measures based on single-cell recording or behavioral methods. The spread of activity based on behavioral methods is in close agreement with the spread based on the direct activation of neurons (as opposed to those activated synaptically). We argue that the greater activation with imaging is attributed to transynaptic spread, which includes sub threshold activation of sites connected to the site of stimulation. The definition of effective current spread therefore depends on the neural event being measured

Over the last two centuries, electrical microstimulation has been used to demonstrate causal links between neural activity and specific behaviors and cognitive functions. However, to establish these links it is imperative to characterize the cortical activity patterns that are elicited by stimulation locally around the electrode and in other functionally connected areas. We have developed a technique to record brain activity using the blood oxygen level dependent (BOLD) signal while applying electrical microstimulation to the primate brain. We find that the spread of activity around the electrode tip in macaque area V1 was larger than expected from calculations based on passive spread of current and therefore may reflect functional spread by way of horizontal connections. Consistent with this functional transynaptic spread we also obtained activation in expected projection sites in extrastriate visual areas, demonstrating the utility of our technique in uncovering in vivo functional connectivity maps.

Classically, three classes of neurons in the cerebellar nuclei (CN), defined by different projection targets and content of transmitters, have been distinguished. However, evidence for different types of neurons based on different intrinsic properties is lacking. The present study reports two types of neurons defined mainly by their intrinsic properties, as determined by whole-cell patch recordings. The majority of cells (type I, n = 63) showed cyclic burst firing whereas a small subset (type II, n = 7) did not. Burst firing was used to distinguish the two types of neurons because, as it turned out, pharmacological interference could not be used to convert the non-bursting cells to bursting ones. Some of the membrane potentials exclusively present in type I neurons, such as sodium and calcium plateau potentials, low-threshold calcium spikes, and a slow calcium-dependent afterhyperpolarization, were found to contribute to the generation of burst firing. Other membrane potentials of type I neurons were not obviously related to the generation of bursts. These were 1) the lower amplitude and width of the action potential during spontaneous activity, 2) a sequence of afterhyperpolarization-afterdepolarization-afterhyperpolarization following each spike, and 3) the high spontaneous firing rate. In contrast, type II neurons lacked slow plateau potentials and low threshold spikes. Their action potentials showed higher amplitude and width and were followed by a single deep afterhyperpolarization. Furthermore, they showed a lower firing rate at rest. In both types of neurons, a delayed inward rectification was present. Neurons filled with neurobiotin revealed that the sizes of the somata and dendritic fields of type I neurons comprised the whole range known from Golgi studies, whereas those of the few type II neurons recovered were found to be in the lowest range. In view of their size and scarcity, we propose that type II neurons may correspond to CN interneurons.

In this study, we applied for the first time a multivariate analysis to describe the anatomy of cerebellar molecular layer interneurons. Forty variables extending over a variety of morphological features (geometrical, topological, and metrical) were obtained from a three-dimensional reconstruction of 26 rat rapid Golgi-stained neurons. The subsequent principal component analysis showed that the first principal component was strongly correlated with variables related to the depth of each cell's soma in the molecular layer. The second principal component was strongly correlated with parameters describing axonal morphology. Finally, an analysis of the distribution of these anatomical features suggested that these cells cannot be classified into distinct groups but, instead, represent one continuously varying population. Thus, the classical division of molecular layer neurons into deep basket cells and superficial stellate cells is not supported by our analysis. These results have important implications for the development of the cerebellar cortex as well as for the expected patterns of Purkinje cell activity following activation of the granule cell layer.