Comprehensive Morpho-Electrotonic Analysis Shows 2 Distinct Classes of L2 and L3 Pyramidal Neurons in Human Temporal Cortex

There have been few quantitative characterizations of the morphological, biophysical, and cable properties of neurons in the human neocortex. We employed feature-based statistical methods on a rare data set of 60 3D reconstructed pyramidal neurons from L2 and L3 in the human temporal cortex (HL2/L3 PCs) removed after brain surgery. Of these cells, 25 neurons were also characterized physiologically. Thirty-two morphological features were analyzed (e.g., dendritic surface area, 36 333 ± 18 157 μm2; number of basal trees, 5.55 ± 1.47; dendritic diameter, 0.76 ± 0.28 μm). Eighteen features showed a significant gradual increase with depth from the pia (e.g., dendritic length and soma radius). The other features showed weak or no correlation with depth (e.g., dendritic diameter). The basal dendritic terminals in HL2/L3 PCs are particularly elongated, enabling multiple nonlinear processing units in these dendrites. Unlike the morphological features, the active biophysical features (e.g., spike shapes and rates) and passive/cable features (e.g., somatic input resistance, 47.68 ± 15.26 MΩ, membrane time constant, 12.03 ± 1.79 ms, average dendritic cable length, 0.99 ± 0.24) were depth-independent. A novel descriptor for apical dendritic topology yielded 2 distinct classes, termed hereby as “slim-tufted” and “profuse-tufted” HL2/L3 PCs; the latter class tends to fire at higher rates. Thus, our morpho-electrotonic analysis shows 2 distinct classes of HL2/L3 PCs.

The dynamics of somatic input processing in spinal motoneurons in vivo

Uncovering how motoneurons utilize their voltage-sensitive conductances to systematically respond to a variety of inputs is paramount to understanding synaptic integration. In this study, we examine the input dynamics and frequency-dependent characteristics of active conductances in motoneurons as viewed from the soma in the decerebrate cat. We evaluated the somatic response of the motoneuron by superimposing a voltage sinus sweep (a sine wave in which frequency increases with time, which is often referred to as a zap or chirp) at a subset of membrane holding potentials during discontinuous, single-electrode, somatic voltage-clamp. Results from both experimental and modeling data indicate that ionic conductances can respond to a wide variety of input dynamics. Notably, it appears that there is a divergence between low input conductance type S and high input conductance type FF motoneurons in their response to input frequency. Type S motoneurons generate a larger response to lower frequency input dynamics (compared with their response to higher frequencies), whereas type FF generate a larger response to higher input frequency dynamics. Functionally, these results may indicate that motoneurons on the lower end of the motor pool (i.e., recruited first) may favor steady inputs, whereas motoneurons at the higher end (i.e., recruited later) may favor input transients in producing action potentials.

Sources of Somatosensory Input to the Caudal Belt Areas of Auditory Cortex

The auditory cortex of nonhuman primates is comprised of a constellation of at least twelve interconnected areas distributed across three major regions on the superior temporal gyrus: core, belt, and parabelt. Individual areas are distinguished on the basis of unique profiles comprising architectonic features, thalamic and cortical connections, and neuron response properties. Recent demonstrations of convergent auditory – somatosensory interactions in the caudomedial (CM) and caudolateral (CL) belt areas prompted us to pursue anatomical studies to identify the source(s) of somatic input to auditory cortex. Corticocortical and thalamocortical connections were revealed by injecting neuroanatomical tracers into CM, CL, and adjoining fields of marmoset ( Callithrix jacchus jacchus) and macaque ( Macaca mulatta) monkeys. In addition to auditory cortex, the cortical connections of CM and CL included somatosensory (retroinsular, Ri; granular insula, Ig) and multisensory areas (temporal parietal occipital, temporal parietal temporal). Thalamic inputs included the medial geniculate complex and several multisensory nuclei (supra- geniculate, posterior, limitans, medial pulvinar), but not the ventroposterior complex. Injections of the core (A1, R) and rostromedial areas of auditory cortex revealed sparse multisensory connections. The results suggest that areas Ri and Ig are the principle sources of somatosensory input to the caudal belt, while multisensory regions of cortex and thalamus may also contribute. The present data add to growing evidence of multisensory convergence in cortical areas previously considered to be ‘unimodal’, and also indicate that auditory cortical areas differ in this respect.

Vagal Input to Lateral Area 3a in Cat Cortex

Penfield's sensory homunculus included visceral organs at its lateral extreme, and vagal input was recently identified lateral to the intraoral representation in primary somatosensory cortex (S1) of rats. We tested whether vagal input is similarly located in cats where area 3b (equivalent to S1) is clearly distinguishable from adjacent regions. Field potentials were recorded from the intact dura over the left hemisphere using electrical stimulation of the left or right cervical vagus nerve in seven cats. A surface positive-negative potential was evoked from either side in the lateral part of the sigmoid gyrus. Finer mapping made at the pial surface with a microelectrode identified a focal site anteromedial to the anterior tip of the coronal sulcus. Depth recordings demonstrated polarity reversals and multi-unit vagal responses, indicating that the potentials were generated by an afferent activation focus in the middle layers of the cortex. The S1 mechanoreceptive representation was localized by mapping multi-unit somatosensory receptive fields in the middle cortical layers near the coronal sulcus. The vagal-evoked potential site was distinctly anterior to the intraoral S1 representation and adjacent to the masseteric-nerve-evoked potential focus. Lesions made at the focal site revealed that this site is cytoarchitectonically located in area 3a not area 3b. Thus vagal input to the sensorimotor cortex in cats resembles deep rather than cutaneous somatic input, similar to the localization of nociceptive-specific input to area 3a in monkeys. The possibilities are considered that this vagal input is involved in motor control and in the sensory experience of visceral afferent activity.

Adaptive Neural Coding Dependent on the Time-Varying Statistics of the Somatic Input Current

It is generally assumed that nerve cells optimize their performance to reflect the statistics of their input. Electronic circuit analogs of neurons require similar methods of self-optimization for stable and autonomous operation. We here describe and demonstrate a biologically plausible adaptive algorithm that enables a neuron to adapt the current threshold and the slope (or gain) of its current-frequency relationship to match the mean (or dc offset) and variance (or dynamic range or contrast) of the time-varying somatic input current. The adaptation algorithm estimates the somatic current signal from the spike train by way of the intracellular somatic calcium concentration, thereby continuously adjusting the neuronś firing dynamics. This principle is shown to work in an analog VLSI-designed silicon neuron.

Spinal Mechanisms Underlying Persistent Pain and Referred Hyperalgesia in Rats With an Experimental Ureteric Stone

Roza, Carolina, Jennifer M. A. Laird, and Fernando Cervero. Spinal mechanisms underlying persistent pain and referred hyperalgesia in rats with an experimental ureteric stone. J. Neurophysiol. 79: 1603–1612, 1998. Spinal neurons processing information from the ureter have been characterized in rats 1–4 days after the implantation of an experimental ureteric stone and compared with those of normal rats. The effects of a conditioning noxious stimulation of the ureter in the presence of the hyperalgesia evoked by the calculosis also were examined. Extracellular recordings were performed at the T12–L1 segments of the spinal cord. In rats with calculosis, more neurons expressed a ureter input (53 vs. 42% in normal rats); such cells being more likely to show background activity, at a higher rate than normals (6.6 ± 1.2 vs. 3.2 ± 0.9 spikes/s; mean ± SE) and increasing with the continuing presence of the stone. The threshold pressure for a ureteric response was higher than in normal rats (79 ± 5 vs. 54 ± 4 mmHg) but the neurons failed to encode increasing intensities of stimulation. Thirty-five percent of the neurons with exclusively innocuous somatic receptive fields had a ureter input in rats with calculosis, whereas none were seen in normal rats. A noxious ureteric distention applied to neurons with ureter input evoked a complex mixture of increases and decreases in somatic receptive field size and/or somatic input properties markedly different from the generalized increases in excitability seen when such a stimulus was applied to normal animals. We conclude that the presence of a ureteric stone evokes excitability changes of spinal neurons (enhanced background activity, greater number of ureter-driven cells, decreased threshold of convergent somatic receptive fields), which likely account for the referred hyperalgesia seen in rats with calculosis. However, further noxious visceral input occurring in the presence of persistent hyperalgesia produces selective changes that cannot be explained by a generalized excitability increase and suggest that the mechanisms underlying maintenance of hyperalgesia include alteration of both central inhibitory and excitatory systems.

Splanchnic and somatic afferent convergence on cervical spinal neurons of the rat

The rostral cervical spinal cord is increasingly being considered the source of important propriospinal regulation. To better understand the substrate for this function, we investigated the effects of stimulation of the greater splanchnic nerve (GSN) and both thoracic and cervical somatic afferents on the activity of cervical spinal neurons. Extracellular single-neuron recordings were made in the C2-C5 spinal segments of chloralose-anesthetized, paralyzed, and artificially ventilated rats. Neurons were classified according to their responses to GSN stimulation. Neurons were inhibited by this stimulation as frequently as they were excited. We then studied the characteristics of cervical and thoracic convergent somatic input to each class of neurons. Although all cervical neurons that responded to GSN stimulation responded to electrical stimulation of the iliohypogastric nerve (IHN), only the few neurons that exhibited whole body receptive fields (RF) responded to natural thoracic somatic stimuli. Responses to electrical stimulation of the GSN and IHN were similar for most neurons; most exhibited nociceptive cutaneous RFs in cervical dermatomes. These data indicate that input from cervical somatic afferents and from both thoracic visceral and thoracic somatic afferents converge on individual splanchnic-receptive cervical neurons. Although these neurons exhibited the predicted cervical somatic RFs, responses from thoracic levels did not exhibit discrete RFs, requiring instead more synchronous or more spatially convergent input.

Processing of splanchnic and somatic input in thoracic spinal cord of the rat

To better understand the spinal transmission of visceral afferent information, we conducted neurophysiological studies of single spinal neurons that receive input from the greater splanchnic nerve (GSN). Extracellular single-neuron recordings were made in the thoracic spinal cord of chloralose-anesthetized, paralyzed, and artificially ventilated rats, some of which had undergone acute spinal transection at C1. Neurons were divided into four classes according to their responses to GSN stimulation: one-burst excitatory, two-burst excitatory, biphasic, and inhibited. We then studied the characteristics of the convergent somatic input to each class of neurons using either natural somatic stimuli or electrical stimulation of the iliohypogastric nerve (IHN). Most splanchnic input was mediated by unmyelinated fibers, whereas somatic input was mediated by both unmyelinated and small myelinated fibers. Most of the neurons exhibited somatic receptive fields, and the majority responded to both innocuous and noxious somatic stimuli. However, a small number could be excited only by GSN stimulation. Although a careful analysis of response characteristics indicated that there was a tendency for neurons to exhibit similar responses to electrical stimulation of the GSN and the IHN, we observed many combinations of somatic and visceral responses. We suggest that visceral afferent activity, in addition to being processed via convergent somatovisceral pathways, may be processed by neurons that convey only visceral information or by neurons in which visceral and somatic information is differentially coded.