Simultaneous Single-unit Recordings Research Articles

Role of the Thalamus in Basal Forebrain Regulation of Neural Activity in the Primary Auditory Cortex.

Many studies have implicated the basal forebrain (BF) as a potent regulator of sensory encoding even at the earliest stages of or cortical processing. The source of this regulation involves the well-documented corticopetal cholinergic projections from BF to primary cortical areas. However, the BF also projects to subcortical structures, including the thalamic reticular nucleus (TRN), which has abundant reciprocal connections with sensory thalamus. Here we present naturalistic auditory stimuli to the anesthetized rat while making simultaneous single-unit recordings from the ventral medial geniculate nucleus (MGN) and primary auditory cortex (A1) during electrical stimulation of the BF. Like primary visual cortex, we find that BF stimulation increases the trial-to-trial reliability of A1 neurons, and we relate these results to change in the response properties of MGN neurons. We discuss several lines of evidence that implicate the BF to thalamus pathway in the manifestation of BF-induced changes to cortical sensory processing and support our conclusions with supplementary TRN recordings, as well as studies in awake animals showing a strong relationship between endogenous BF activity and A1 reliability. Our findings suggest that the BF subcortical projections that modulate MGN play an important role in auditory processing.

Frequency-specific coupling in fronto-parieto-occipital cortical circuits underlie active tactile discrimination

Processing of tactile sensory information in rodents is critically dependent on the communication between the primary somatosensory cortex (S1) and higher-order integrative cortical areas. Here, we have simultaneously characterized single-unit activity and local field potential (LFP) dynamics in the S1, primary visual cortex (V1), anterior cingulate cortex (ACC), posterior parietal cortex (PPC), while freely moving rats performed an active tactile discrimination task. Simultaneous single unit recordings from all these cortical regions revealed statistically significant neuronal firing rate modulations during all task phases (anticipatory, discrimination, response, and reward). Meanwhile, phase analysis of pairwise LFP recordings revealed the occurrence of long-range synchronization across the sampled fronto-parieto-occipital cortical areas during tactile sampling. Causal analysis of the same pairwise recorded LFPs demonstrated the occurrence of complex dynamic interactions between cortical areas throughout the fronto-parietal-occipital loop. These interactions changed significantly between cortical regions as a function of frequencies (i.e. beta, theta and gamma) and according to the different phases of the behavioral task. Overall, these findings indicate that active tactile discrimination by rats is characterized by much more widespread and dynamic complex interactions within the fronto-parieto-occipital cortex than previously anticipated.

Ovine model of neuropathic pain for assessing mechanisms of spinal cord stimulation therapy via dorsal horn recordings, von Frey filaments, and gait analysis.

BackgroundIt is becoming increasingly important to understand the mechanisms of spinal cord stimulation (SCS) in alleviating neuropathic pain as novel stimulation paradigms arise.PurposeAdditionally, the small anatomic scale of current SCS animal models is a barrier to more translational research.MethodsUsing chronic constriction injury (CCI) of the common peroneal nerve (CPN) in sheep (ovine), we have created a chronic model of neuropathic pain that avoids motor deficits present in prior large animal models. This large animal model has allowed us to implant clinical grade SCS hardware, which enables both acute and chronic testing using von Frey filament thresholds and gait analysis. Furthermore, the larger anatomic scale of the sheep allows for simultaneous single-unit recordings from the dorsal horn and SCS with minimal electrical artifact.ResultsDetectable tactile hypersensitivity occurred 21 days after nerve injury, with preliminary indications that chronic SCS may reverse it in the painful limb. Gait analysis revealed no hoof drop in the CCI model. Single neurons were identified and discriminated in the dorsal horn, and their activity was modulated via SCS. Unlike previous large animal models that employed a complete transection of the nerve, no motor deficit was observed in the sheep with CCI.ConclusionTo our knowledge, this is the first reported large animal model of chronic neuropathic pain which facilitates the study of both acute and chronic SCS using complementary behavioral and electrophysiologic measures. As demonstrated by our successful establishment of these techniques, an ovine model of neuropathic pain is suitable for testing the mechanisms of SCS.

In vitro single-unit recordings reveal increased peripheral nerve conduction velocity by focused pulsed ultrasound

Ultrasound that is widely used in medical diagnosis has drawn growing interests as a noninvasive means of neuromodulation. Focused pulsed ultrasound (FPUS) effectively modulates neural encoding and transmission in the peripheral nervous system (PNS) with unclear mechanism of action, which is further confounded by contradictory experimental outcomes from recordings of compound action potentials (CAP). To address that, we developed a novel in vitro set up to achieve simultaneous single-unit recordings from individual mouse sciatic nerve axon and systematically studied the neuromodulation effects of FPUS on individual axon. Unlike previous CAP recordings, our single-unit recordings afford superior spatial and temporal resolution to reveal the subtle but consistent effects of ultrasonic neuromodulation. Our results indicate that, (1) FPUS did not evoke action potentials directly in mouse sciatic nerve at all the tested intensities (spatial peak temporal average intensity, ISPTA of 0.91 to 28.2 W/cm2); (2) FPUS increases the nerve conduction velocity (CV) in both fast-conducting A- and slow-conducting C- type axons with effects more pronounced at increased stimulus duration and intensity; and (3) effects of increased CV is reversible and cannot be attributed to the change of local temperature. Our results support existing theories of non-thermal mechanisms underlying ultrasonic neuromodulation with low-intensity FPUS, including NICE, flexoelectricity, and solition models. This work also provides a solid experimental basis to further advance our mechanistic understandings of ultrasonic neuromodulation in the PNS.

In vitro multichannel single-unit recordings of action potentials from the mouse sciatic nerve

Electrode arrays interfacing with peripheral nerves are essential for neuromodulation devices targeting peripheral organs to relieve symptoms. To modulate (i.e., single-unit recording and stimulating) individual peripheral nerve axons remains a technical challenge. Here, we report an in vitro setup to allow simultaneous single-unit recordings from multiple mouse sciatic nerve axons. The sciatic nerve (∼30 mm) was harvested and transferred to a tissue chamber, the ∼5 mm distal end pulled into an adjacent recording chamber filled with paraffin oil. A custom-built multi-wire electrode array was used to interface with split fine nerve filaments. Single-unit action potentials were evoked by electrical stimulation and recorded from 186 axons, of which 49.5% were classed A-type with conduction velocities (CV) greater than 1 m s−1 and 50.5% were C-type (CV < 1 m s−1). The single-unit recordings had no apparent bias towards A- or C-type axons, were robust and repeatable for over 60 min, and thus an ideal opportunity to assess different neuromodulation strategies targeting peripheral nerves. For instance, ultrasonic modulation of action potential transmission was assessed using the setup, indicating increased nerve conduction velocity following ultrasound stimulus. This setup can also be used to objectively assess the design of next-generation electrode arrays interfacing with peripheral nerves.

Scalable, Lightweight, Integrated and Quick-to-Assemble (SLIQ) Hyperdrives for Functional Circuit Dissection.

Independently adjustable multielectrode arrays are routinely used to interrogate neuronal circuit function, enabling chronic in vivo monitoring of neuronal ensembles in freely behaving animals at a single-cell, single spike resolution. Despite the importance of this approach, its widespread use is limited by highly specialized design and fabrication methods. To address this, we have developed a Scalable, Lightweight, Integrated and Quick-to-assemble multielectrode array platform. This platform additionally integrates optical fibers with independently adjustable electrodes to allow simultaneous single unit recordings and circuit-specific optogenetic targeting and/or manipulation. In current designs, the fully assembled platforms are scalable from 2 to 32 microdrives, and yet range 1–3 g, light enough for small animals. Here, we describe the design process starting from intent in computer-aided design, parameter testing through finite element analysis and experimental means, and implementation of various applications across mice and rats. Combined, our methods may expand the utility of multielectrode recordings and their continued integration with other tools enabling functional dissection of intact neural circuits.

Retinal and Nonretinal Contributions to Extraclassical Surround Suppression in the Lateral Geniculate Nucleus

Extraclassical surround suppression is a prominent receptive field property of neurons in the lateral geniculate nucleus (LGN) of the dorsal thalamus, influencing stimulus size tuning, response gain control, and temporal features of visual responses. Despite evidence for the involvement of both retinal and nonretinal circuits in the generation of extraclassical suppression, we lack an understanding of the relative roles played by these pathways and how they interact during visual stimulation. To determine the contribution of retinal and nonretinal mechanisms to extraclassical suppression in the feline, we made simultaneous single-unit recordings from synaptically connected retinal ganglion cells and LGN neurons and measured the influence of stimulus size on the spiking activity of presynaptic and postsynaptic neurons. Results show that extraclassical suppression is significantly stronger for LGN neurons than for their retinal inputs, indicating a role for extraretinal mechanisms. Further analysis revealed that the enhanced suppression can be accounted for by mechanisms that suppress the effectiveness of retinal inputs in evoking LGN spikes. Finally, an examination of the time course for the onset of extraclassical suppression in the LGN and the size-dependent modulation of retinal spike efficacy suggests the early phase of augmented suppression involves local thalamic circuits. Together, these results demonstrate that the LGN is much more than a simple relay for retinal signals to cortex; it also filters retinal spikes dynamically on the basis of stimulus statistics to adjust the gain of visual signals delivered to cortex. <b>SIGNIFICANCE STATEMENT</b> The lateral geniculate nucleus (LGN) is the gateway through which retinal information reaches the cerebral cortex. Within the LGN, neuronal responses are often suppressed by stimuli that extend beyond the classical receptive field. This form of suppression, called extraclassical suppression, serves to adjust the size tuning, response gain, and temporal response properties of neurons. Given the important influence of extraclassical suppression on visual signals delivered to cortex, we performed experiments to determine the circuit mechanisms that contribute to extraclassical suppression in the LGN. Results show that suppression is augmented beyond that provided by direct retinal inputs and delayed, consistent with polysynaptic inhibition. Importantly, these mechanisms influence the effectiveness of incoming retinal signals, thereby filtering the signals ultimately conveyed to cortex.

Retinal and Nonretinal Contributions to Extraclassical Surround Suppression in the Lateral Geniculate Nucleus.

The lateral geniculate nucleus (LGN) is the gateway through which retinal information reaches the cerebral cortex. Within the LGN, neuronal responses are often suppressed by stimuli that extend beyond the classical receptive field. This form of suppression, called extraclassical suppression, serves to adjust the size tuning, response gain, and temporal response properties of neurons. Given the important influence of extraclassical suppression on visual signals delivered to cortex, we performed experiments to determine the circuit mechanisms that contribute to extraclassical suppression in the LGN. Results show that suppression is augmented beyond that provided by direct retinal inputs and delayed, consistent with polysynaptic inhibition. Importantly, these mechanisms influence the effectiveness of incoming retinal signals, thereby filtering the signals ultimately conveyed to cortex.

Temporal correlation mechanisms and their role in feature selection: a single-unit study in primate somatosensory cortex.

Author SummaryAttention can select stimuli in space based on the stimulus features most relevant for a task. Attention effects have been linked to several important phenomena such as modulations in neuronal spiking rate (i.e., the average number of spikes per unit time) and spike-spike synchrony between neurons. Attention has also been associated with spike count correlations, a measure that is thought to reflect correlated noise in the population of neurons. Here, we studied whether feature-based attention biases the correlated activity between neurons when attention is directed towards their common preferred feature. Simultaneous single-unit recordings were obtained from multiple neurons in secondary somatosensory cortex in non-human primates performing feature-attention tasks. Both firing rate and spike-synchrony were enhanced when attention was directed towards the preferred feature of cells. However, attention effects on spike-synchrony had a tighter relationship with behavior. Further, attention decreased spike-count correlations when it was directed towards the receptive field of cells. Our data indicate that temporal correlation codes play a role in mediating feature selection, and are consistent with a feature-based selection model that operates by reducing the overall noise in a population and synchronizing activity across subpopulations that encode the relevant features of sensory stimuli.

Prefrontal single-unit firing associated with deficient extinction in mice

The neural circuitry mediating fear extinction has been increasingly well studied and delineated. The rodent infralimbic subregion (IL) of the ventromedial prefrontal cortex (vmPFC) has been found to promote extinction, whereas the prelimbic cortex (PL) demonstrates an opposing, pro-fear, function. Studies employing in vivo electrophysiological recordings have observed that while increased IL single-unit firing and bursting predicts robust extinction retrieval, increased PL firing can correlate with sustained fear and poor extinction. These relationships between single-unit firing and extinction do not hold under all experimental conditions, however. In the current study, we further investigated the relationship between vmPFC and PL single-unit firing and extinction using inbred mouse models of intact (C57BL/6J, B6) and deficient (129S1/SvImJ, S1) extinction strains. Simultaneous single-unit recordings were made in the PL and vmPFC (encompassing IL) as B6 and S1 mice performed extinction training and retrieval. Impaired extinction retrieval in S1 mice was associated with elevated PL single-unit firing, as compared to firing in extinguishing B6 mice, consistent with the hypothesized pro-fear contribution of PL. Analysis of local field potentials also revealed significantly higher gamma power in the PL of S1 than B6 mice during extinction training and retrieval. In the vmPFC, impaired extinction in S1 mice was also associated with exaggerated single-unit firing, relative to B6 mice. This is in apparent contradiction to evidence that IL activity promotes extinction, but could reflect a (failed) compensatory effort by the vmPFC to mitigate fear-promoting activity in other regions, such as the PL or amygdala. In support of this hypothesis, augmenting IL activity via direct infusion of the GABAA receptor antagonist picrotoxin rescued impaired extinction retrieval in S1 mice. Chronic fluoxetine treatment produced modest reductions in fear during extinction retrieval and increased the number of Zif268-labeled cells in layer II of IL, but failed to increase vmPFC single-unit firing. Collectively, these findings further support the important contribution these cortical regions play in determining the balance between robust extinction on the one hand, and sustained fear on the other. Elucidating the precise nature of these roles could help inform understanding of the pathophysiology of fear-related anxiety disorders.

The Spatial Structure of Stimuli Shapes the Timescale of Correlations in Population Spiking Activity

Throughout the central nervous system, the timescale over which pairs of neural spike trains are correlated is shaped by stimulus structure and behavioral context. Such shaping is thought to underlie important changes in the neural code, but the neural circuitry responsible is largely unknown. In this study, we investigate a stimulus-induced shaping of pairwise spike train correlations in the electrosensory system of weakly electric fish. Simultaneous single unit recordings of principal electrosensory cells show that an increase in the spatial extent of stimuli increases correlations at short () timescales while simultaneously reducing correlations at long () timescales. A spiking network model of the first two stages of electrosensory processing replicates this correlation shaping, under the assumptions that spatially broad stimuli both saturate feedforward afferent input and recruit an open-loop inhibitory feedback pathway. Our model predictions are experimentally verified using both the natural heterogeneity of the electrosensory system and pharmacological blockade of descending feedback projections. For weak stimuli, linear response analysis of the spiking network shows that the reduction of long timescale correlation for spatially broad stimuli is similar to correlation cancellation mechanisms previously suggested to be operative in mammalian cortex. The mechanism for correlation shaping supports population-level filtering of irrelevant distractor stimuli, thereby enhancing the population response to relevant prey and conspecific communication inputs.

Thalamic synchrony and the adaptive gating of information flow to cortex

Although it has long been posited that sensory adaptation serves to enhance information flow in sensory pathways, the neural basis remains elusive. Simultaneous single–unit recordings in the thalamus and cortex in anesthetized rats reveal that adaptation differentially influences thalamus and cortex in a manner that fundamentally changes the nature of information conveyed about vibrissae motion. Utilizing an ideal observer of cortical activity, performance in detecting vibrissa deflections degrades with adaptation, while performance in discriminating between vibrissa deflections of different velocities is enhanced, a trend not observed in thalamus. Analysis of simultaneously recorded thalamic neurons does reveal, however, an analogous adaptive change in thalamic synchrony that mirrors the cortical response. An integrate–and–fire model using experimentally measured thalamic input reproduces the observed transformations. The results here suggest a shift in coding strategy with adaptation that directly controls information relayed to cortex, which could have implications for encoding velocity signatures of textures.

Rapid Changes in Thalamic Firing Synchrony during Repetitive Whisker Stimulation

Thalamic firing synchrony is thought to ensure selective transmission of relevant sensory information to the recipient cortical neurons by rendering them more responsive to temporally correlated input spikes. However, direct evidence for a synchrony code in the thalamus is limited. Here, we directly measure thalamic firing synchrony and its stimulus-induced modulation over time, using simultaneous single unit recordings from individual thalamic barreloids in the rat somatosensory whisker/barrel system. Employing whisker deflections varying in velocity or frequency and a cross-correlation approach, we find systematic changes in both time course and strength of thalamic firing synchrony as a function of stimulus parameters and sensory adaptation. Synchrony develops faster and is greater with higher velocity deflections. Greater firing synchrony reflects stimulus-dependent increases in instantaneous firing rates, greater spike time precision relative to stimulus onset as well as common input that likely arises from divergent trigeminothalamic and corticothalamic neurons. With adaptation, synchrony decreases and takes longer to develop but is more dependent on the cells' common inputs. Rapid, sharp increases in thalamic synchrony mirroring quick increases in whisker velocity occur also during ongoing random, high-frequency whisker vibrations. Together, results demonstrate millisecond by millisecond changes in thalamic near-synchronous firing during complex patterns of ongoing vibrissa movements that may ensure transmission of preferred sensory information in local thalamocortical circuits during whisking and active touch.

Mapping Prefrontal CircuitsIn Vivowith Manganese-Enhanced Magnetic Resonance Imaging in Monkeys

Manganese-enhanced magnetic resonance imaging (MEMRI) provides a powerful tool to study multisynaptic circuits in vivo and thereby to link information about neural structure and function within individual subjects. Making the best use of MEMRI in monkeys requires minimizing manganese-associated neurotoxicity, maintaining sensitivity to manganese-dependent signal changes and mapping transport throughout the brain without a priori anatomical hypotheses. Here, we performed intracortical injections of isotonic MnCl(2), comparisons of preinjection and postinjection scans, and voxelwise statistical mapping. Isotonic MnCl(2) did not cause cell death at the injection site, damage to downstream targets of manganese transport, behavioral deficits, or changes in neuronal responsiveness. We detected and mapped manganese transport throughout cortical-subcortical circuits by using voxelwise statistical comparisons of at least 10 preinjection and two postinjection scans. We were able to differentiate between focal and diffuse projection fields and to distinguish between the topography of striatal projections from orbitofrontal and anterior cingulate cortex in a single animal. This MEMRI approach provides a basis for combining circuit-based anatomical analyses with simultaneous single-unit recordings and/or functional magnetic resonance imaging in individual monkeys. Such studies will enhance our interpretations of functional data and our understanding of how neuronal activity is transformed as it propagates through a circuit.

Detecting synfire chain activity using massively parallel spike train recording.

The synfire chain model has been proposed as the substrate that underlies computational processes in the brain and has received extensive theoretical study. In this model cortical tissue is composed of a superposition of feedforward subnetworks (chains) each capable of transmitting packets of synchronized spikes with high reliability. Computations are then carried out by interactions of these chains. Experimental evidence for synfire chains has so far been limited to inference from detection of a few repeating spatiotemporal neuronal firing patterns in multiple single-unit recordings. Demonstration that such patterns actually come from synfire activity would require finding a meta organization among many detected patterns, as yet an untried approach. In contrast we present here a new method that directly visualizes the repetitive occurrence of synfire activity even in very large data sets of multiple single-unit recordings. We achieve reliability and sensitivity by appropriately averaging over neuron space (identities) and time. We test the method with data from a large-scale balanced recurrent network simulation containing 50 randomly activated synfire chains. The sensitivity is high enough to detect synfire chain activity in simultaneous single-unit recordings of 100 to 200 neurons from such data, enabling application to experimental data in the near future.

Dependent multivariate diffusion models and related point process models of ensemble spiking neurons

The first-passage time of a diffusion process through a constant or variable boundary has been the focus of many stochastic models of neuronal membrane potential dynamics. Diffusion processes have been used extensively to model a latent process that may only be observable through consequent renewal point process events. The mathematical relationship between inter-spike intervals and the first-passage time of simple diffusion models is well-known, however this relationship becomes increasingly more complex as the diffusion models become more physiologically realistic, and when multivariate diffusion processes are no longer considered to be independent. The probability density of a diffusing particle position at a particular point in time P(x, t) as defined by the Fokker-Planck equation can be solved, under suitable conditions, using the method of images. We show how the method of images can be extended to a multivariate probability density constructed from marginal densities modeling simple individual spiking neurons using a copula construction that factors out the correlated (dependent) noise structure. This in turn provides a straightforward method for estimating multivariate spike survival and hazard functions from simultaneously recorded single unit activity and, indirectly, the ensemble neuron diffusion noise dependence. The analytical approach is supported by simulated Wiener processes with drift and applied to simultaneous single unit recordings from Heschl's gyrus in awake human subjects. Extensions of this approach to more physiologically realistic diffusion models such as the Ornstein-Uhlenbeck and Feller processes will be discussed.

Searching for “the Top” in Top-Down Control

Although numerous theoretical models implicate the prefrontal cortex (PFC) as a source of top-down control signals, empirical support is limited. In this review, we highlight direct evidence for this view of PFC function and discuss several lines of other supportive findings. Most evidence to-date is only suggestive due to methodological challenges in tracking the spatiotemporal dynamics of cortical networks. However, we discuss several promising approaches that could further our understanding of the role of the PFC in goal-directed behavior.

Striatal Inhibition of Nociceptive Responses Evoked in Trigeminal Sensory Neurons by Tooth Pulp Stimulation

The noxious evoked response in trigeminal sensory neurons was studied to address the role of striatum in the control of nociceptive inputs. In urethane-anesthetized rats, the jaw opening reflex (JOR) was produced by suprathreshold stimulation of the tooth pulp and measured as electromyographic response in the digastric muscle, with simultaneous recording of noxious responses in single unit neurons of the spinal trigeminal nucleus pars caudalis (Sp5c). The microinjection of glutamate (80 etamol/0.5 microl) into striatal JOR inhibitory sites significantly decreased the A delta and C fiber-mediated-evoked response (53 +/- 4.2 and 43.6 +/- 6.4% of control value, P < 0.0001) in 92% (31/34) of nociceptive Sp5c neurons. The microinjection of the solvent was ineffective, as was microinjection of glutamate in sites out of the JOR inhibitory ones. In another series of experiments, simultaneous single unit recordings were performed in the motor trigeminal nucleus (Mo5) and the Sp5c nucleus. Microinjection of glutamate decreased the noxious-evoked response in Sp5c and Mo5 neurons in parallel with the JOR, without modifying spontaneous neuronal activity of trigeminal motoneurons (n = 8 pairs). These results indicate that the striatum could be involved in the modulation of nociceptive inputs and confirm the role of the basal ganglia in the processing of nociceptive information.

Simultaneous Single Unit Recording in the Mitral Cell Layer of the Rat Olfactory Bulb under Nasal and Tracheal Breathing

Odor perception depends on the odorant-evoked changes on Mitral/Tufted cell firing pattern within the olfactory bulb (OB). The OB exhibits a significant "ongoing" or spontaneous activity in the absence of sensory stimulation. We characterized this ongoing activity by simultaneously recording several single neurons in the mitral cell layer (MCL) of anesthetized rats and determined the extent of synchrony and oscillations under nasal and tracheal breathing. We recorded 115 neurons and found no significant differences in the mean firing rates between both breathing conditions. Surprisingly, nearly all single units exhibited a long refractory period averaging 14.4 ms during nasal respiration that was not different under tracheal breathing. We found a small incidence (2% of neurons) of gamma band oscillations and a low incidence (8.1%) of correlated firing between adjacent MCL cells. During nasal respiration, a significant oscillation at the respiratory rate was observed in 12% of cells that disappeared during tracheal breathing. Thus, in the absence of odorants, MCL cells exhibit a long refractory period, probably reflecting the intrinsic OB network properties. Furthermore, in the absence of sensory stimulation, MCL cell discharge does not oscillate in the gamma band and the respiratory cycle can modulate the firing of these cells.

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. Here, we studied the effects of increased PBR input on the spatial receptive field properties of cells in the dLGN. We made simultaneous single-unit recordings of the input to the cells from the retina (S-potentials) and the output of the cells to the cortex (action potentials) to determine spatial receptive field modifications generated in the dLGN. State-dependent modulation of the spatial receptive field properties was studied by electrical stimulation of the PBR. The results showed that PBR stimulation had only a minor effect on the modifications of the spatial receptive field properties generated in the dLGN. The PBR-evoked effects could be described mainly as increased response gain. This suggested that the spatial modifications of the receptive field occurred at an earlier stage of processing in the dLGN than the PBR-controlled gain regulation, such that the PBR input modulates the gain of the spatially modified signals. We propose that the spatial receptive field modifications occur at the input to relay cells through the synaptic triades between retinal afferents, inhibitory interneurone dendrites, and relay cell dendrites and that the gain regulation is related to postsynaptic cholinergic effects on the relay cells.