Computational role of large receptive fields in the primary somatosensory cortex.

Computational studies are challenging the intuitive view that neurons with broad tuning curves are necessarily less discriminative than neurons with sharp tuning curves. In the context of somatosensory processing, broad tuning curves are equivalent to large receptive fields. To clarify the computational role of large receptive fields for cortical processing of somatosensory information, we recorded ensembles of single neurons from the infragranular forelimb/forepaw region of the rat primary somatosensory cortex while tactile stimuli were separately delivered to different locations on the forelimbs/forepaws under light anesthesia. We specifically adopted the perspective of individual columns/segregates receiving inputs from multiple body location. Using single-trial analyses of many single-neuron responses, we obtained two main results. 1) The responses of even small populations of neurons recorded from within the same estimated column/segregate can be used to discriminate between stimuli delivered to different surround locations in the excitatory receptive fields. 2) The temporal precision of surround responses is sufficiently high for spike timing to add information over spike count in the discrimination between surround locations. This surround spike-timing code (i) is particularly informative when spike count is ambiguous, e.g., in the discrimination between close locations or when receptive fields are large, (ii) becomes progressively more informative as the number of neurons increases, (iii) is a first-spike code, and (iv) is not limited by the assumption that the time of stimulus onset is known. These results suggest that even though large receptive fields result in a loss of spatial selectivity of single neurons, they can provide as a counterpart a sophisticated temporal code based on latency differences in large populations of neurons without necessarily sacrificing basic information about stimulus location.

Proprioceptive and cutaneous representations in the rat ventral posterolateral thalamus.

Determining how and where proprioceptive information is represented in the rat ventral posterolateral (VPL) is important in allowing us to further investigate how this sense is utilized during motor control and learning. Here we demonstrate using electrophysiological techniques that the rostral portion of the rat VPL nucleus (rVPL, -2 to -2.5 mm bregma) carries a large amount of proprioceptive information. Caudal to this region is a zone where the cutaneous receptive fields are focal (mVPL for middle VPL, -2.5 to -3.2 mm bregma) with a fine topographic map of the fore- and hindlimbs. The forepaw is represented with digit 1 medial and each subsequent digit increasingly lateral, all of which are dorsal to the pads. The caudal VPL (cVPL, -3.2 to -4.0 mm bregma) has broad receptive fields and is the target of lamina 1 and lamina 2, as well as the dorsal column nuclei, and may represent the flow of nociceptive information through the VPL. Thus we propose that the VPL may be thought of as three subnuclei-the rostral, middle, and caudal VPL-each carrying preferentially a different modality of information. This pattern of information flow through the rat VPL is similar, although apparently rotated, to that of many primates, indicating that these regions in the rat (rVPL, mVPL, and cVPL) have become further differentiated in primates where they are seen as separate nuclei (VPS, VPL, and VPI/VMpo).

Influence of norepinephrine on somatosensory neuronal responses in the rat thalamus: a combined modeling and in vivo multi-channel, multi-neuron recording study.

Norepinephrine released within primary sensory circuits from locus coeruleus afferent fibers can produce a spectrum of modulatory actions on spontaneous or sensory-evoked activity of individual neurons. Within the ventral posterior medial thalamus, membrane currents modulated by norepinephrine have been identified. However, the relationship between the cellular effects of norepinephrine and the impact of norepinephrine release on populations of neurons encoding sensory signals is still open to question. To address this lacuna in understanding the net impact of the noradrenergic system on sensory signal processing, a computational model of the rat trigeminal somatosensory thalamus was generated. The effects of independent manipulation of different cellular actions of norepinephrine on simulated afferent input to the computational model were then examined. The results of these simulations aided in the design of in vivo neural ensemble recording experiments where sensory-driven responses of thalamic neurons were measured before and during locus coeruleus activation in waking animals. Together the simulated and experimental results reveal several key insights regarding the regulation of neural network operation by norepinephrine including: 1) cell-specific modulatory actions of norepinephrine, 2) mechanisms of norepinephrine action that can improve the tuning of the network and increase the signal-to-noise ratio of cellular responses in order to enhance network representation of salient stimulus features and 3) identification of the dynamic range of thalamic neuron function through which norepinephrine operates.

Beta- and gamma-frequency coupling between olfactory and motor brain regions prior to skilled, olfactory-driven reaching.

A major question in neuroscience concerns how widely separated brain regions coordinate their activity to produce unitary cognitive states or motor actions. To investigate this question, we employed multisite, multielectrode recording in rats to study how olfactory and motor circuits are coupled prior to the execution of an olfactory-driven, GO/NO-GO variant of a skilled, rapidly executed (approximately 350-600 ms) reaching task. During task performance, we recorded multi-single units and local field potentials (LFPs) simultaneously from the rats' olfactory cortex (specifically, the posterior piriform cortex) and from cortical and subcortical motor sites (the caudal forepaw M1, and the magnocellular red nucleus, respectively). Analyses on multi-single units across areas revealed an increase in beta-frequency spiking (12-30 Hz) during a approximately 100 ms window surrounding the Final Sniff of the GO cue before lifting the arm (the "Sniff-GO window") that was seldom seen when animals sniffed the NO-GO cue. Also during the Sniff-GO window, LFPs displayed a striking increase in beta, low-gamma, and high-gamma energy (12-30, 30-50, and 50-100 Hz, respectively), and oscillations in the high gamma band appeared to be coherent across the recorded sites. These results indicate that transient, multispectral coherence across cortical and subcortical brain sites is part of the coordination process prior to sensory-guided movement initiation.

The reach-to-grasp-food task for rats: a rare case of modularity in animal behavior?

Humans and non-human animals make use of sensory hierarchies in "selecting" strategies for solving many cognitive and behavioral tasks. Often, if a preferred type of sensory information is unavailable or is not useful for solving a given task, the animal can switch to a lower-priority strategy, making use of a different class of sensory information. In the case of rats performing a classic reach-to-grasp-food task, however, prior studies indicate that the reaching maneuver may be a fixed action pattern that is guided exclusively by the food's odor plume until the point of contact with the food morsel [Whishaw IQ, Tomie JA. Olfaction directs skilled forelimb reaching in the rat. Behav Brain Res 1989;32(1):11-21; Metz GA, Whishaw IQ. Skilled reaching an action pattern: stability in rat (Rattus norvegicus) grasping movements as a function of changing food pellet size. Behav Brain Res 2000;116(2):111-22; Whishaw IQ. Did a change in sensory control of skilled movements stimulate the evolution of the primate frontal cortex? Behav Brain Res 2003;146(1/2):31-41]. We sought to confirm and extend these findings in several ways. In Experiment 1, using a GO/NO-GO variant of the classic task, we demonstrated that rats used the GO target's odor both to trigger and guide their reaches. In Experiment 2, we showed that rats deprived of (a) vision, (b) object-recognizing rostral whiskers and forearm sinus hairs, or (c) both, displayed no deficits in triggering and guiding their reaches. Finally, in a third experiment in which the GO target's location varied randomly across trials and only olfactory cues were available, we demonstrated that rats could determine the spatial endpoint of their reach without any loss of accuracy. Combined with results from a prior study in which bulbectomized rats never developed a new, successful reaching strategy despite extensive post-operative training [Whishaw IQ, Tomie JA. Olfaction directs skilled forelimb reaching in the rat. Behav Brain Res 1989;32(1):11-21], these results indicate that rats do not have a sensory hierarchy for solving the reach-to-grasp-food task, but rather, are guided by olfaction alone until their paw contacts the food morsel.

Neural ensemble activity from multiple brain regions predicts kinematic and dynamic variables in a multiple force field reaching task.

In everyday life, we reach, grasp, and manipulate a variety of different objects all with their own dynamic properties. This degree of adaptability is essential for a brain-controlled prosthetic arm to work in the real world. In this study, rats were trained to make reaching movements while holding a torque manipulandum working against two distinct loads. Neural recordings obtained from arrays of 32 microelectrodes spanning the motor cortex were used to predict several movement related variables. In this paper, we demonstrate that a simple linear regression model can translate neural activity into endpoint position of a robotic manipulandum even while the animal controlling it works against different loads. A second regression model can predict, with 100% accuracy, which of the two loads is being manipulated by the animal. Finally, a third model predicts the work needed to move the manipulandum endpoint. This prediction is significantly better than that for position. In each case, the regression model uses a single set of weights. Thus, the neural ensemble is capable of providing the information necessary to compensate for at least two distinct load conditions.

Rapid learning and flexible memory in "habit" tasks in rats trained with brain stimulation reward.

Two groups of rats, one rewarded with sweetened food and the other rewarded with medial forebrain bundle (MFB) stimulation, were trained to home in on and dig for a buried object coated with a target odor. After each group had 15 training trials, MFB rats searched with greater accuracy and speed than food-rewarded rats. MFB rats were subsequently tested (1) after 6 weeks with no additional practice; (2) with food or non-food distractor odors, and (3) with major spatial alterations to the search environment, and in all cases searched with the same high accuracy, short search time, and low level of distractibility as in baseline. These results suggest that the high motivation provided by MFB reward engenders rapidly formed, long-lasting, and surprisingly flexibly deployable "habit" memories.

Force field apparatus for investigating movement control in small animals.

As part of our overall effort to build a closed loop brain-machine interface (BMI), we have developed a simple, low weight, and low inertial torque manipulandum that is ideal for use in motor system investigations with small animals such as rats. It is inexpensive and small but emulates features of large and very expensive systems currently used in monkey and human research. Our device consists of a small programmable torque-motor system that is attached to a manipulandum. Rats are trained to grasp this manipulandum and move it to one or more targets against programmed force field perturbations. Here we report several paradigms that may be used with this device and results from rat's making reaching movements in a variety of force fields. These and other available experimental manipulations allow one to experimentally separate several key variables that are critical for understanding and ultimately emulating the feedforward and feedback mechanisms of motor control.

Ceramic-based multisite electrode arrays for chronic single-neuron recording.

A method is described for the manufacture of a microelectrode array for chronic, multichannel, single neuron recording. The ceramic-based, multisite electrode array has four recording sites patterned onto a ceramic shaft the size of a single typical microwire electrode. The sites and connecting wires are applied to the ceramic substrate using a reverse photolithographic procedure. Recording sites (22 x 80 microm) are separated by 200 microm along the shaft. A layer of alumina insulation is applied over the whole array (exclusive of recording sites) by ion-beam assisted deposition. These arrays were capable of recording single neuron activity from each of their recording sites for at least three weeks during chronic implantation in the somatosensory cortex of rats, and several sites had recordings that lasted for more than 8 weeks. The vertical arrangement of the recording sites on these electrodes is ideal for simultaneously recording across the different layers of brain areas such as the cerebral cortex and hippocampus in chronic preparations.

Using multi-neuron population recordings for neural prosthetics.

Classical single-neuron recording methods led to 'neuron-centric' concepts of neural coding, whereas more recent multi-neuron population recordings have inspired 'population-centric' concepts of distributed processing in neural systems. Because most neocortical neurons code information coarsely, sensory or motor processing tends to be widely distributed across neuronal populations. Dynamic fluctuations in neural population functions thus involve subtle changes in the overall pattern of neural activity. Mathematical analysis of neural population codes allows extraction of 'motor signals' from neuronal population recordings in the motor cortices, which can then be used in real-time to directly control movement of a robot arm. This technique holds promise for the development of neurally controlled prosthetic devices and provides insights into how information is distributed across several brain regions.

A multi-channel telemetry system for brain microstimulation in freely roaming animals.

A system is described that enables an experimenter to remotely deliver electrical pulse train stimuli to multiple different locations in the brains of freely moving rats. The system consists of two separate components: a transmitter base station that is controlled by a PC operator, and a receiver-microprocessor integrated pack worn on the back of the animals and which connects to suitably implanted brain locations. The backpack is small and light so that small animal subjects can easily carry it. Under remote command from the PC the backpack can be configured to provide biphasic pulse trains of arbitrarily specified parameters. A feature of the system is that it generates precise brain-stimulation behavioral effects using the direct constant-voltage TTL output of the backpack microprocessor. The system performs with high fidelity even in complex environments over a distance of about 300 m. Rat self-stimulation tests showed that this system produced the same behavioral responses as a conventional constant-current stimulator. This system enables a variety of multi-channel brain stimulation experiments in freely moving animals. We have employed it to develop a new animal behavior model ("virtual" conditioning) for the neurophysiological study of spatial learning, in which a rat can be accurately guided to navigate various terrains.

Rat navigation guided by remote control.

Free animals can be 'virtually' trained by microstimulating key areas of their brains.