Monosynaptic Excitation Research Articles

Input-output organization of inhibitory neurons in the interstitial nucleus of Cajal projecting to the contralateral trochlear and oculomotor nucleus

Neurons in the interstitial nucleus of Cajal (INC) that are known to be involved in eye and head movements are excitatory. We investigated the input-output organization of inhibitory INC neurons involved in controlling vertical saccades. Intracellular recordings were made in INC neurons activated antidromically by stimulation of the contralateral trochlear or oculomotor nucleus, and their synaptic input properties from the superior colliculi (SCs) and the contralateral INC were analyzed in anesthetized cats. Many INC neurons projected to the contralateral trochlear nucleus, Forel's field H, INC, and oculomotor nucleus, and mainly received monosynaptic excitation followed by disynaptic inhibition from the ipsi- and contralateral SCs. After sectioning the commissural connections between the SCs, these neurons received monosynaptic excitation from the ipsilateral medial SC and disynaptic inhibition via the INC from the contralateral lateral SC. Another group of INC neurons were antidromically activated from the contralateral oculomotor nucleus, INC and Forel's field H, but not from the trochlear nucleus, and received monosynaptic excitation from the ipsilateral lateral SC and disynaptic inhibition from the contralateral medial SC. The former group was considered to inhibit contralateral trochlear and inferior rectus motoneurons in upward saccades, whereas the latter was considered to inhibit contralateral superior rectus and inferior oblique motoneurons in downward saccades. The mutual inhibition existed between these two groups of INC neurons for upward saccades on one side and downward saccades on the other. This pattern of input-output organization of inhibitory INC neurons suggests that the basic neural circuits for horizontal and vertical saccades are similar.

眼球運動制御系における上丘間抑制性及び興奮性交連結合の性質について

The superior colliculus serves to orient an animal to a target in the opposite visual hemifield. Commissural connections between the bilateral superior colliculi (SCs) are known to help maintain visual fixation and suppress saccades. Sprague (1966) showed that after transection of the commissure between the SCs, cats that had been made blind by prior ablation of the occipitotemporal cortex once again visually oriented to objects in a hemifield. This outcome, called the Sprague effect, suggests that the commissural connection of the SC may play an important role in visual-orienting behavior, and may mediate mutual suppression between the two SCs to prevent competing responses in the opposite direction.Later electrophysiological studies confirmed the inhibitory nature of the commissural tectotectal projection. Our recent study, using intracellular recording combined with electrical stimulation of the SC, showed that tectoreticular neurons (TRNs) in the caudal ‘saccade zone’ mainly received monosynaptic inhibition from the contralateral rostral SC and mono- or disynaptic inhibition from its caudal part, whereas TRNs in the rostral SC received monosynaptic excitation from the contralateral rostral SC, and mono- or disynaptic inhibition from all rostrocaudal levels of the contralateral SC. This review summarizes the characteristic features of commissural inhibition and excitation between the two SCs on various output TRNs terminating on different kinds of interneurons in the horizontal saccade generator in the brainstem of the cat.

Requirement of neuronal connexin36 in pathways mediating presynaptic inhibition of primary afferents in functionally mature mouse spinal cord

Electrical synapses formed by gap junctions containing connexin36 (Cx36) promote synchronous activity of interneurones in many regions of mammalian brain; however, there is limited information on the role of electrical synapses in spinal neuronal networks. Here we show that Cx36 is widely distributed in the spinal cord and is involved in mechanisms that govern presynaptic inhibition of primary afferent terminals. Electrophysiological recordings were made in spinal cord preparations from 8- to 11-day-old wild-type and Cx36 knockout mice. Several features associated with presynaptic inhibition evoked by conditioning stimulation of low threshold hindlimb afferents were substantially compromised in Cx36 knockout mice. Dorsal root potentials (DRPs) evoked by low intensity stimulation of sensory afferents were reduced in amplitude by 79% and in duration by 67% in Cx36 knockouts. DRPs were similarly affected in wild-types by bath application of gap junction blockers. Consistent with presynaptic inhibition of group Ia muscle spindle afferent terminals on motoneurones described in adult cats, conditioning stimulation of an adjacent dorsal root evoked a long duration inhibition of monosynaptic reflexes recorded from the ventral root in wild-type mice, and this inhibition was antagonized by bicuculline. The same conditioning stimulation failed to inhibit monosynaptic reflexes in Cx36 knockout mice. Immunofluorescence labelling for Cx36 was found throughout the dorsal and ventral horns of the spinal cord of juvenile mice and persisted in mature animals. In deep dorsal horn laminae, where interneurones involved in presynaptic inhibition of large diameter muscle afferents are located, cells were extensively dye-coupled following intracellular neurobiotin injection. Coupled cells displayed Cx36-positive puncta along their processes. Our results indicate that gap junctions formed by Cx36 in spinal cord are required for maintenance of presynaptic inhibition, including the regulation of transmission from Ia muscle spindle afferents. In addition to a role in presynaptic inhibition in juvenile animals, the persistence of Cx36 expression among spinal neuronal populations in the adult mouse suggests that the contribution of electrical synapses to integrative processes in fully mature spinal cord may be as diverse as that found in other areas of the CNS.

Neural substrate for suppression of omnipause neurons at the onset of saccades

The saccade trigger signal was proposed by D.A. Robinson, but neural substrates for triggering saccades by inhibiting omnipause neuron (OPN) activity still remain controversial. We investigated tectal inputs to OPNs by recording intracellular potentials from OPNs and inhibitory burst neurons (IBNs) and searched for interneurons to inhibit OPNs in the brainstem of anesthetized cats. IBNs received monosynaptic excitation from the contralateral caudal superior colliculus (SC) and disynaptic inhibition via contralateral IBNs from the ipsilateral caudal SC, whereas IBNs received disynaptic inhibition from the rostral SC. The latter disynaptic inhibition was mediated by OPNs, since OPNs received monosynaptic excitation from the rostral SC and projected to IBNs. In contrast, OPNs received disynaptic inhibition from the caudal SC. This disynaptic inhibition from the caudal SC was mediated to OPNs by IBNs. These findings suggested possible roles of IBNs for triggering and maintaining saccades by actively inhibiting the tonic activity of OPNs.

Control of CA3 Output by Feedforward Inhibition Despite Developmental Changes in the Excitation–Inhibition Balance

In somatosensory cortex, the relative balance of excitation and inhibition determines how effectively feedforward inhibition enforces the temporal fidelity of action potentials. Within the CA3 region of the hippocampus, glutamatergic mossy fiber (MF) synapses onto CA3 pyramidal cells (PCs) provide strong monosynaptic excitation that exhibit prominent facilitation during repetitive activity. We demonstrate in the juvenile CA3 that MF-driven polysynaptic IPSCs facilitate to maintain a fixed EPSC-IPSC ratio during short-term plasticity. In contrast, in young adult mice this MF-driven polysynaptic inhibitory input can facilitate or depress in response to short trains of activity. Transgenic mice lacking the feedback inhibitory loop continue to exhibit both facilitating and depressing polysynaptic IPSCs, indicating that this robust inhibition is not caused by the secondary engagement of feedback inhibition. Surprisingly, eliminating MF-driven inhibition onto CA3 pyramidal cells by blockade of GABA(A) receptors did not lead to a loss of temporal precision of the first action potential observed after a stimulus but triggered in many cases a long excitatory plateau potential capable of triggering repetitive action potential firing. These observations indicate that, unlike other regions of the brain, the temporal precision of single MF-driven action potentials is dictated primarily by the kinetics of MF EPSPs, not feedforward inhibition. Instead, feedforward inhibition provides a robust regulation of CA3 PC excitability across development to prevent excessive depolarization by the monosynaptic EPSP and multiple action potential firings.

Complementary spatial firing in place cell-interneuron pairs

The hippocampal formation plays a pivotal role in representing the physical environment. While CA1 pyramidal cells display sharply tuned location-specific firing, the activity of many interneurons show weaker but significant spatial modulation. Although hippocampal interneurons were proposed to participate in the representation of space, their interplay with pyramidal cells in formation of spatial maps is not well understood. In this study, we investigated the spatial correlation between CA1 pyramidal cells and putative interneurons recorded concurrently in awake rats. Positively and negatively correlated pairs were found to be simultaneously present in the CA1 region. While pyramidal cell-interneuron pairs with positive spatial correlation showed similar firing maps, negative spatial correlation was often accompanied by complementary place maps, which could occur even in the presence of a monosynaptic excitation between the cells. Thus, location-specific firing increase of hippocampal interneurons is not necessarily a simple product of excitation by a pyramidal cell with a similarly positioned firing field. Based on our observation of pyramidal cells firing selectively in the low firing regions of interneurons, we speculate that the location-specific firing of place cells is partly determined by the location-specific decrease of interneuron activity that can release place cells from inhibition.

Brief Bursts Self-Inhibit and Correlate the Pyramidal Network

Author SummaryThe neocortex of the mammalian brain contains many more excitatory neurons than inhibitory neurons, yet inhibitory neurons are essential components of neocortical circuitry. Inhibitory neurons form dense and intricate connections with excitatory neurons, which are mainly pyramidal cells. One prominent pathway formed between pyramidal cells and inhibitory Martinotti cells is frequency-dependent disynaptic inhibition (FDDI), which mediates a strong inhibitory signal in the microcircuitry of the neocortex. Here, we reveal deeper insight into how FDDI is mediated and recruited within the circuit, showing that short simultaneous bursts in four pyramidal cells are sufficient to exert FDDI in all neighboring pyramidal cells within the dimensions of a cortical column. As few as three synchronous action potentials in three pyramidal cells can trigger FDDI. This powerful inhibition is mediated by only a few inhibitory neurons yet correlates membrane potential fluctuations, leading to synchronous spiking between pyramidal cells that simultaneously receive FDDI. The inhibitory signals are independent and electrically isolated from excitation mediated by neighboring PCs via basal dendrites. We propose FDDI as an important pathway that is readily activated by brief bursts of action potentials and correlates neocortical network activity.

Reliable Coding Emerges from Coactivation of Climbing Fibers in Microbands of Cerebellar Purkinje Neurons

The inferior olive projects climbing fiber axons to cerebellar Purkinje neurons, where they trigger calcium-based dendritic spikes. These responses dynamically shape the immediate spike output of Purkinje cells as well as provide an instructive signal to guide long-term plasticity. Climbing fibers typically fire approximately once a second, and the instructive role is distributed over many such firing events. However, transmission of salient information on an immediate basis needs to occur on a shorter timescale during which a Purkinje cell would typically be activated by a climbing fiber only once. Here we show using in vivo calcium imaging in anesthetized mice and rats that sensory events are rapidly and reliably represented by momentary, simultaneous coactivation of microbands of adjacent Purkinje cells. Microbands were sagittally oriented and spanned up to 100 microm mediolaterally, representing hundreds of Purkinje cells distributed over multiple folia. Spontaneous and sensory-evoked microbands followed boundaries that were close or identical to one another and were desynchronized by olivary injection of the gap junction blocker mefloquine, indicating that excitation to the olive is converted to synchronized firing by electrical coupling. One-time activation of microbands could distinguish a sensory response from spontaneous activity with up to 98% accuracy. Given the anatomy of the olivocerebellar system, microband synchrony may shape the output of neurons in the cerebellar nuclei either via powerful inhibition by Purkinje cells or by direct monosynaptic excitation from the inferior olive.

Is Sensory Processing about Detecting Abrupt Changes in the Sensory World?

Event Abstract Back to Event Is Sensory Processing about Detecting Abrupt Changes in the Sensory World? One of the most salient properties of the sensory system is its propensity to respond strongly to transient rather than to static stimuli. This marked preference for changes is found in the brain at all levels. A variety of mechanisms are known to boost responses to higher temporal frenquencies such as short-term synaptic depression, spike rate adaptation and feedforward inhibition. However, change detection as a major role of sensory processing remains largely unexplored. In order to test this hypothesis, we use a novel probabilistic framework and show quantitatively the importance of feedfoward inhibition in detecting sudden "appearance" (or "desappearance") of stimuli. Assuming a Markov dynamics of stimuli, we derive an "ideal observer" that computes on-line a probability of a sudden change in input firing rates (a transition). In general, this model predicts a bi-phasic, non-linear synaptic integration consisting of a fast, transient, excitation followed by a slower inhibition. The same stimulus that excites the cell at short delays inhibits it at longer ones. However, the exact properties of this integration, in particular the strength and time constants of excitation and inhibition depend on the temporal statistics of the stimulus and the reliability of the input spike trains : in noisier settings, longer integrations are required to detect changes. We explore what this general framework implies for temporal receptive fields (tRFs), contrast adaptation and spike-time precision in early visual areas. We suppose that output spikes are generated when the probability of transition crosses a threshold, followed by a refractory period. This spike generation mechanism reproduces the firing statistics in the retina and LGN in response to time varying stimuli. Particularly sharp peaks in PSTH that could not be predicted directly from the linear tRFs, but instead could be obtained by adding feedforward inhibition and refractoriness. The predicted tRFs resemble the ones of "ON" and "OFF" retinal ganglion cells and LGN cells, but their shape adapts to the (variance of the) contrast of the input. At low contrast, integration dominates, resulting in a slower, mainly excitatory tRFs. At high contrast, tRFs are shorter and more strongly biphasic, similar to temporal derivatives. This adaptation emerges naturally from the non-linear probabilistic equations. Moreover, we found that bursts of spikes are preceded by strong inhibition while single spikes are not. We, next, use this model to investigate biophysical implementations of change detection and propose a specific neural mechanism based on synaptic short-term plasticity. We consider a small microcircuit commonly observed in many sensory areas, namely a pyramidal neuron receiving both mono-synaptic excitation from another pyramidal "source" cell and disynaptic inhibition from the same source cell. If the excitatory synapse is depressing and the inhibitory one facilitating, parameters of this biophysical system can be adjusted to approach the ideal performance. We compare this prediction with recent experimental data. Conference: Computational and systems neuroscience 2009, Salt Lake City, UT, United States, 26 Feb - 3 Mar, 2009. Presentation Type: Poster Presentation Topic: Poster Presentations Citation: (2009). Is Sensory Processing about Detecting Abrupt Changes in the Sensory World?. Front. Syst. Neurosci. Conference Abstract: Computational and systems neuroscience 2009. doi: 10.3389/conf.neuro.06.2009.03.351 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 10 Feb 2009; Published Online: 10 Feb 2009. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Google Google Scholar PubMed Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Seeking functions for spinal recurrent inhibition

In this issue of The Journal of Physiology, Lamy et al. (2008) describe a rhythmic modulation of recurrent inhibition during walking in man. This provides some insight into the function of recurrent inhibition, first described by Renshaw (1941) as an inhibition of cat motoneurones produced by antidromic stimulation of the axons of neighbouring motoneurones (homonymous action). Subsequent work, also in cats, showed that motor axon collaterals activate interneurones (the eponymous Renshaw cells) that in turn inhibit motoneurones. Actions extend to more distant muscle groups (heteronymous) and parallel the pattern of heteronymous monosynaptic excitation from muscle spindle Ia afferents. Renshaw cells receive peripheral sensory and descending inputs and have output connections to other spinal interneurones and to other Renshaw cells. So recurrent inhibition is more than just negative feedback from and to motoneurones and may have several functions depending upon motor context. Lamy et al. have focused on heteronymous actions (which are more widespread in man than in cats or monkeys) in the context of our unique bipedal form of walking. The knee extensor quadriceps is a source of recurrent inhibition to the ankle extensor and the flexor muscles soleus and tibialis anterior. But given that these ankle muscles are antagonists, how is differential activation achieved? The authors found that around heel strike and early in stance, when quadriceps is active and soleus activity is increasing, recurrent inhibition of soleus is weak. Conversely, later in stance, when quadriceps is active and soleus activity is declining, recurrent inhibition of soleus is strong. Recurrent inhibition of tibialis anterior motoneurones was neither task nor phase dependent. The reduction in soleus recurrent inhibition would assist the transition from swing to stance and enhanced inhibition later in stance would favour the transition from stance to swing by reducing reciprocal inhibition of tibialis anterior. The origin of these changes in recurrent inhibition remains uncertain but activity of peripheral sensory or descending motor pathways could be involved. Two interesting possibilities are the corticospinal pathway, known to depress homonymous recurrent inhibition of soleus in sitting subjects (Mazzocchio et al. 1994) and the vestibulospinal pathway that depresses recurrent inhibition of soleus in standing stance (Iles & Pisini, 1992). It might be possible to extend such studies to heteronymous actions in walking stance. More meticulous experiments built upon the framework of human research protocols pioneered by the Paris group will likely increase our understanding of recurrent inhibition even further.

Frequency-Independent Synaptic Transmission Supports a Linear Vestibular Behavior

The vestibular system is responsible for transforming head motion into precise eye, head, and body movements that rapidly stabilize gaze and posture. How do central excitatory synapses mediate behavioral outputs accurately matched to sensory inputs over a wide dynamic range? Here we demonstrate that vestibular afferent synapses in vitro express frequency-independent transmission that spans their in vivo dynamic range (5-150 spikes/s). As a result, the synaptic charge transfer per unit time is linearly related to vestibular afferent activity in both projection and intrinsic neurons of the vestibular nuclei. Neither postsynaptic glutamate receptor desensitization nor saturation affect the relative amplitude or frequency-independence of steady-state transmission. Finally, we show that vestibular nucleus neurons can transduce synaptic inputs into linear changes in firing rate output without relying on one-to-one calyceal transmission. These data provide a physiological basis for the remarkable linearity of vestibular reflexes.

Differential Inhibitory Control of Semicircular Canal Nerve Afferent-Evoked Inputs in Second-Order Vestibular Neurons by Glycinergic and GABAergic Circuits

Labyrinthine nerve-evoked monosynaptic excitatory postsynaptic potentials (EPSPs) in second-order vestibular neurons (2 degrees VN) sum with disynaptic inhibitory postsynaptic potentials (IPSPs) that originate from the thickest afferent fibers of the same nerve branch and are mediated by neurons in the ipsilateral vestibular nucleus. Pharmacological properties of the inhibition and the interaction with the afferent excitation were studied by recording monosynaptic responses of phasic and tonic 2 degrees VN in an isolated frog brain after electrical stimulation of individual semicircular canal nerves. Specific transmitter antagonists revealed glycine and GABA(A) receptor-mediated IPSPs with a disynaptic onset only in phasic but not in tonic 2 degrees VN. Compared with GABAergic IPSPs, glycinergic responses in phasic 2 degrees VN have larger amplitudes and a longer duration and reduce early and late components of the afferent nerve-evoked subthreshold activation and spike discharge. The difference in profile of the disynaptic glycinergic and GABAergic inhibition is compatible with the larger number of glycinergic as opposed to GABAergic terminal-like structures on 2 degrees VN. The increase in monosynaptic excitation after a block of the disynaptic inhibition in phasic 2 degrees VN is in part mediated by a N-methyl-d-aspartate receptor-activated component. Although inhibitory inputs were superimposed on monosynaptic EPSPs in tonic 2 degrees VN as well, the much longer latency of these IPSPs excludes a control by short-latency inhibitory feed-forward side-loops as observed in phasic 2 degrees VN. The differential synaptic organization of the inhibitory control of labyrinthine afferent signals in phasic and tonic 2 degrees VN is consistent with the different intrinsic signal processing modes of the two neuronal types and suggests a co-adaptation of intrinsic membrane properties and emerging network properties.

Auditory nerve inputs to cochlear nucleus neurons studied with cross-correlation

The strength of synapses between auditory nerve (AN) fibers and ventral cochlear nucleus (VCN) neurons is an important factor in determining the nature of neural integration in VCN neurons of different response types. Synaptic strength was analyzed using cross-correlation of spike trains recorded simultaneously from an AN fiber and a VCN neuron in anesthetized cats. VCN neurons were classified as chopper, primarylike, and onset using previously defined criteria, although onset neurons usually were not analyzed because of their low discharge rates. The correlograms showed an excitatory peak (EP), consistent with monosynaptic excitation, in AN–VCN pairs with similar best frequencies (49% 24/49 of pairs with best frequencies within ±5%). Chopper and primarylike neurons showed similar EPs, except that the primarylike neurons had shorter latencies and shorter-duration EPs. Large EPs consistent with end bulb terminals on spherical bushy cells were not observed, probably because of the low probability of recording from one. The small EPs observed in primarylike neurons, presumably spherical bushy cells, could be derived from small terminals that accompany end bulbs on these cells. EPs on chopper or primarylike-with-notch neurons were consistent with the smaller synaptic terminals on multipolar and globular bushy cells. Unexpectedly, EPs were observed only at sound levels within about 20 dB of threshold, showing that VCN responses to steady tones shift from a 1:1 relationship between AN and VCN spikes at low sound levels to a more autonomous mode of firing at high levels. In the high level mode, the pattern of output spikes seems to be determined by the properties of the postsynaptic spike generator rather than the input spike patterns. The EP amplitudes did not change significantly when the presynaptic spike was preceded by either a short or long interspike interval, suggesting that synaptic depression and facilitation have little effect under the conditions studied here.

The importance of the cortico-motoneuronal system for control of grasp.

Our recent work has revealed new evidence of the importance of direct cortico-motoneuronal (CM) connections for voluntary control of the hand. Most of these connections are derived from corticospinal neurons located in the M1 hand area, although there are some much smaller contributions from other secondary motor areas, such as the supplementary motor area (SMA). Intracellular recordings show that 75% of upper limb motoneurons in the chloralose-anaesthetized macaque monkey receive a monosynaptic projection from the corticospinal tract; evidence for non-monosynaptic, propriospinal excitatory influences from the corticospinal tract was conspicuously lacking in these anaesthetized preparations. Moreover, in the conscious monkey, hand and arm muscle motor unit responses to corticospinal tract input are dominated by single, brief peaks compatible with monosynaptic excitation. CM excitatory post-synaptic potentials, recorded from a comparable sample of hand and arm motoneurons in anaesthetized macaque and squirrel monkeys, were found to be larger and faster rising in the macaque, which is by far the more dexterous of the two species. CM cells facilitating a given muscle in the conscious macaque are distributed over a wide region of M1 cortex, and each contributes a particular pattern of discharge during a skilled task. In addition to their direct effects on target muscles there may be weaker but potentially important effects that derive from the synchronous binding of assemblies of output neurons. Synchronous oscillations between these neurons are particularly prevalent during steady grip, but disappear during digit movement.

Functional studies of motor cortex.

Defining functions for neural elements becomes more difficult the more remote they are, in synaptic linkages, from motor neurons. The precentral motor cortex contains a corticomotoneuronal projection system, only one synapse removed from motor neurons. Corticomotoneuronal fibres produce monosynaptic excitation of spinal motor neurons, which is more powerful for those acting distally, innervating extensor muscles of the fingers and intrinsic hand muscles. Latencies and time-course of corticomotoneuronal excitation are defined. Amplitudes of unitary corticomotoneuronal excitatory postsynaptic potentials are very small. Many corticomotoneuronal cells converge on a given motor neuron. Some motor neurons innervating proximally acting muscles appear to receive no corticomotoneuronal excitation. Disynaptic inhibitory actions are produced by corticospinal volleys via the common Ia inhibitory interneuron--possibly reciprocal actions produced over collaterals of corticomotoneuronal fibres. Anatomical divergence of projections of collaterals of an identified corticomotoneuronal fibre is extensive enough to provide both for delivery of synapses to a large number of motor neurons and for the dispersion of specific projections to inhibitory interneurons, to fusimotor neurons and to other interneurons. Functions of corticomotoneuronal elements in motor cortex whose targets have been identified and whose excitatory or inhibitory actions have been specified by cross-correlation have been studied by Fetz & Cheney (J Neurophysiol 1980; 44:751-772).

Commissural Mirror-Symmetric Excitation and Reciprocal Inhibition Between the Two Superior Colliculi and Their Roles in Vertical and Horizontal Eye Movements

The functional roles of commissural excitation and inhibition between the two superior colliculi (SCs) are not yet well understood. We previously showed the existence of strong excitatory commissural connections between the rostral SCs, although commissural connections had been considered to be mainly inhibitory. In this study, by recording intracellular potentials, we examined the topographical distribution of commissural monosynaptic excitation and inhibition from the contralateral medial and lateral SC to tectoreticular neurons (TRNs) in the medial or lateral SC of anesthetized cats. About 85% of TRNs examined projected to both the ipsilateral Forel's field H and the contralateral inhibitory burst neuron region where the respective premotor neurons for vertical and horizontal saccades reside. Medial TRNs received strong commissural excitation from the medial part of the opposite SC, whereas lateral TRNs received excitation mainly from its lateral part. Injection of wheat germ agglutinin-horseradish peroxidase into the lateral or medial SC retrogradely labeled many larger neurons in the lateral or medial part of the contralateral SC, respectively. These results indicated that excitatory commissural connections exist between the medial and medial parts and between the lateral and lateral parts of the rostral SCs. These may play an important role in reinforcing the conjugacy of upward and downward saccades, respectively. In contrast, medial SC projections to lateral SC TRNs and lateral SC projections to medial TRNs mainly produce strong inhibition. This shows that regions representing upward saccades inhibit contralateral regions representing downward saccades and vice versa.

Neural Organization of the Pathways From the Superior Colliculus to Trochlear Motoneurons

The neural organization of the pathways from the superior colliculus (SC) to trochlear motoneurons was analyzed in anesthetized cats using intracellular recording and transneuronal labeling techniques. Stimulation of the ipsilateral or contralateral SC evoked excitation and inhibition in trochlear motoneurons with latencies of 1.1-2.3 and 1.1-3.8 ms, respectively, suggesting that the earliest components of excitation and inhibition were disynaptic. A midline section between the two SCs revealed that ipsi- and contralateral SC stimulation evoked disynaptic excitation and inhibition in trochlear motoneurons, respectively. Premotor neurons labeled transneuronally after application of wheat germ agglutinin-conjugated horseradish peroxidase into the trochlear nerve were mainly distributed ipsilaterally in the Forel's field H (FFH) and bilaterally in the interstitial nucleus of Cajal (INC). Consequently, we investigated these two likely intermediaries between the SC and trochlear nucleus electrophysiologically. Stimulation of the FFH evoked ipsilateral mono- and disynaptic excitation and contralateral disynaptic inhibition in trochlear motoneurons. Preconditioning stimulation of the ipsilateral SC facilitated FFH-evoked monosynaptic excitation. Stimulation of the INC evoked ipsilateral monosynaptic excitation and inhibition, and contralateral monosynaptic inhibition in trochlear motoneurons. Preconditioning stimulation of the contralateral SC facilitated contralateral INC-evoked monosynaptic inhibition. These results revealed a reciprocal input pattern from the SCs to vertical ocular motoneurons in the saccadic system; trochlear motoneurons received disynaptic excitation from the ipsilateral SC via ipsilateral FFH neurons and disynaptic inhibition from the contralateral SC via contralateral INC neurons. These inhibitory INC neurons were considered to be a counterpart of inhibitory burst neurons in the horizontal saccadic system.

VPM and PoM Nuclei of the Rat Somatosensory Thalamus: Intrinsic Neuronal Properties and Corticothalamic Feedback

Sensory information originating in individual whisker follicles ascends through focused projections to the brainstem, then to the ventral posteromedial nucleus (VPM) of the thalamus, and finally into barrels of the primary somatosensory cortex (S1). By contrast, the posteromedial complex (PoM) of the thalamus receives more diffuse sensory projections from the brainstem and projects to the interbarrel septa of S1. Both VPM and PoM receive abundant corticothalamic projections from S1. Using a thalamocortical slice preparation, we characterized differences in intrinsic neuronal properties and in responses to corticothalamic feedback in neurons of VPM and PoM. Due to the plane of the slice, the majority of our observed responses came from activation of layer VI because most or all of the layer V axons terminating in PoM are cut. We found that VPM neurons exhibit higher firing rates than PoM neurons when stimulated with injected current. Stimulation of corticothalamic fibers evoked monosynaptic excitation, disynaptic inhibition, or a combination of the two in both nuclei. A few differences in the feedback responses emerged: purely excitatory postsynaptic potentials (EPSPs) in VPM were smaller and facilitated more than those in PoM, and only the EPSPs in VPM had a strong NMDA component. For both nuclei, some of the feedback responses were purely disynaptic inhibitory postsynaptic potentials (IPSPs) from the thalamic reticular nucleus (TRN). This was due to EPSP failures within VPM and PoM combined with greater reliability of S1-originating synapses onto TRN. These findings suggest that despite the exclusively excitatory nature of corticothalamic fibers, activation of cortex can trigger excitation or inhibition in thalamic relay neurons.

Respiratory drive to thoracic motoneurones

The paper by Saywell et al. (2007) in this issue of The Journal of Physiology provides a detailed study of the projection of the expiratory bulbospinal neurones to identified thoracic motoneurones in the anaesthetized cat. The importance of the paper lies first in its clarification of the debate regarding the strength of the monosynaptic excitation from this pathway and secondly, the deduction of the significance of the pathway in driving natural rhythmic motoneurone firing. The methods developed and the conclusions derived are relevant not only to the special case of respiration, but also to the more general consideration of the part played by particular sources of excitation in generating motoneurone firing patterns in other systems. It has long been known that both the inspiratory and the expiratory phases of breathing are dependent on activity in groups of cells in the hindbrain (Pitts et al. 1939). The most extensively studied group are in the nucleus retroambigualis and their output is carried to various motoneurones involved in respiration via crossed bulbospinal fibres. Previous studies have indicated that both phrenic and inspiratory intercostal motoneurones receive monosynaptic excitation from this source, but probably depend to a large degree on multisynaptic connections for their natural firing pattern (Davies et al. 1985). The relative contributions of mono- and multisynaptic connections to expiratory motoneurones, on the other hand, have not been clear. Using intracellular spike-triggered averaging (STA) from expiratory bulbospinal neurones (EBSNs) to internal intercostal motoneurones Merrill & Lipski (1987) found only very few and weak monosynaptic excitatory postsynaptic potentials (EPSPs), which could account for neither the rhythmic motoneurone firing nor the observed central respiratory drive potentials (CRDPs). Cross-correlation of EBSN spikes with expiratory nerve filaments also rarely showed the short duration peak expected for a monosynaptic connection. It was surprising therefore that when a spike correlation study was repeated by Kirkwood (1995) most EBSN neurones showed clear evidence of monosynaptic projection, which was estimated to be producing most of the depolarization required to drive the rhythmic firing of the expiratory motoneurones. A valuable review of this background was provided by Kirkwood et al. (1999) together with preliminary data now reported in detail. This new study has confirmed, by intracellular STA, the presence of a potent monosynaptic connection, especially to expiratory neurones with their axons in the internal intercostal nerves. Computations, taking account of directly measured EPSP duration and amplitude and reasonable estimates of numbers of EBSNs and of their firing frequencies, indicate that the sum of the unitary EPSPs could account for the observed CRDPs. Indeed the data imply a projection at least 10 times as strong as that found by Merrill & Lipski (1987). Of course the question arises as to how there can be such a disparity in data from basically similar experiments. Factors such as bias in selection of motoneurone types, rostral or caudal recording sites in a segment or variation according to the part of the thorax supplied were all considered but rejected. A final possibility arises from the observation of a correlation between EPSP size and CRDP amplitude, which suggests that some state-dependent modulation in EPSP amplitude may vary between different preparations, for example as a result of differing anaesthesia. Although the same agent (pentobarbitone) was employed in both cases, Saywell et al. (2007) appear to have controlled the dosage to give a lighter level. Nevertheless, this seems unlikely to be a very important factor and other causes should be considered. It is worth recalling the observations of Nelson et al. (1979) showing acute increases in Ia EPSP amplitudes following spinal transection. The mechanism of such state-dependent modulation is not considered, but two factors might be examined in future work. There could well be a presynaptic inhibitory mechanism involved (see Rudomin & Schmidt, 1999) which could vary due to small differences in the preparation. Also, the incidence of failures of transmission (Grimwood et al. 1992) could differ according to the condition of the animal. It is interesting to speculate as to the functional significance of a potentially strong monosynaptic EBSN projection to expiratory motoneurones. We have come to associate monosynaptic descending control with the need for precision, as in hand movements in primates. Perhaps similar precision may be required in some expiratory movements such as vocalization (Sears, 1977), though cats are not noted for their musical skills. The more serious message is the importance of detailed quantitative studies, such as reported by Saywell et al. (2007) in establishing the relative significance for normal function of various neural projections, which are generally only established qualitatively.

Neural Pathways for Vertical Saccades: From the Superior Colliculus to Trochlear Motoneurons

The pathways from the superior colliculus (SC) to vertical ocular motoneurons were analyzed in anesthetized cats using intracellular recording from trochlear motoneurons. Electrical stimulation of the ipsilateral or contralateral SC evoked disynaptic excitation and inhibition in trochlear motoneurons. Stimulation of the ipsilateral Forel's field H (FFH) and the contralateral interstitial nucleus of Cajal (INC) evoked monosynaptic excitation and inhibition in trochlear motoneurons, respectively. Preconditioning stimulation of the SC facilitated FFH-evoked monosynaptic excitation. The results showed that trochlear motoneurons receive disynaptic excitation via the FFH from the ipsilateral SC and disynaptic inhibition via the INC from the contralateral SC.