Warren E. Foote

Striate cortex increases contrast gain of macaque LGN neurons

Recurrent projections comprise a universal feature of cerebral organization. Here, we show that the corticofugal projections from the striate cortex (VI) to the lateral geniculate nucleus (LGN) robustly and multiplicatively enhance the responses of parvocellular neurons, stimulated by gratings restricted to the classical receptive field and modulated in luminance, by over two-fold in a contrast-independent manner at all but the lowest contrasts. In the equiluminant plane, wherein stimuli are modulated in chromaticity with luminance held constant, such enhancement is strongly contrast dependent. These projections also robustly enhance the responses of magnocellular neurons but contrast independently only at high contrasts. Thus, these results have broad functional significance at both network and neuronal levels by providing the experimental basis and quantitative constraints for a wide range of models on recurrent projections and the control of contrast gain.

Retinal afferents to the dorsal raphe nucleus in rats and Mongolian gerbils

A direct pathway from the retina to the dorsal raphe nucleus (DRN) has been demonstrated in both albino rats and Mongolian gerbils. Following intraocular injection of cholera toxin subunit B (CTB), a diffuse stream of CTB‐positive, fine‐caliber optic axons emerged from the optic tract at the level of the pretectum/anterior mesencephalon. In gerbils, CTB‐positive axons descended ventromedially into the periaqueductal gray, moving caudally and arborizing extensively throughout the DRN. In rats, the retinal‐DRN projection comprised fewer, but larger caliber, axons, which arborized in a relatively restricted region of the lateral and ventral DRN. Following injection of CTB into the lateral DRN, retrogradely labeled ganglion cells (GCs) were observed in whole‐mount retinas of both species. In gerbils, CTB‐positive GCs were distributed over the entire retina, and a nearest‐neighbor analysis of CTB‐positive GCs showed significant regularity (nonrandomness) in their distribution. The overall distribution of gerbil GC soma diameters ranged from 8 to 22 μm and was skewed slightly towards the larger soma diameters. Based on an adaptive mixtures model statistical analysis, two Gaussian distributions appeared to comprise the total GC distribution, with mean soma diameters of 13 (SEM ±1.7) μm, and 17 (SEM ±1.5) μm, respectively. In rats, many fewer CTB‐positive GCs were labeled following CTB injections into the lateral DRN, and nearly all occurred in the inferior retina. The total distribution of rat GC soma diameters was similar to that in gerbils and also was skewed towards the larger soma diameters. Major differences observed in the extent and configuration of the retinal‐DRN pathway may be related to the diurnal/crepuscular vs. nocturnal habits of these two species. J. Comp. Neurol. 414:469–484, 1999.

The distribution of substance P-containing neurons in the cat Edinger-Westphal nucleus: relationship to efferent projection systems

The light microscopic localization of substance P-like immunoreactivity (SPLI) was examined in the cat Edinger--Westphal complex using the peroxidase--antiperoxidase method. A high density of cell bodies and processes staining for SPLI were found in the caudal part of the Edinger--Westphal complex (EWc) capping the somatic divisions of the oculomotor nucleus. This distribution continued rostrally into the anteromedian nucleus (AM). Cells labeled with SPLI were also found arranged in a thin layer dorsally capping the oculomotor nucleus, and scattered cells were found in the periaqueductal gray region at the same level. This distribution of SPLI-positive cells was then compared with the distribution of cells in EWc and AM that are retrogradely labeled by horseradish peroxidase or Nuclear Yellow injections into spinal cord, cerebellum, or ciliary ganglion. Injections of horseradish peroxidase into both cervical and lumbar cord labeled a large number of cells throughout the length of EWc and the more rostral AM. A similar pattern of labeling was seen following injections of Nuclear Yellow into the deep cerebellar nuclei. In contrast, cells innervating the ciliary ganglion were found predominantly outside of the Edinger--Westphal complex in AM, the rostral periaqueductal region, and the tegmentum ventral to the oculomotor complex. The distribution of cells projecting to spinal cord or cerebellum and the pattern of SPLI staining was found to closely overlap, evidence that substance P may be contained in cells that give rise to the central projections of the Edinger--Westphal complex.

Edinger-Westphal neurons that project to spinal cord contain substance P

Combined retrograde transport and immunocytochemical methods were used to determine whether Edinger-Westphal neurons projecting to spinal cord also demonstrate substance P-like immunoreactivity (SPLI). Large injections of horseradish peroxidase (HRP) into cervical and lumbar enlargements retrogradely labeled cells throughout the length of the Edinger-Westphal complex (EW). Nearly all HRP-labeled EW neurons also stained for SPLI, evidence that EW is the origin of a direct substance P pathway linking rostral mesencephalon with spinal cord.

Effect of midbrain raphe and lateral mesencephalic stimulation on spontaneous and evoked activity in the lateral geniculate of the cat.

SummarySingle shock stimulation of the midbrain raphe and lateral reticular formation altered the spontaneous and evoked activity of single cells in the dorsal lateral geniculate of the cat. The effect of stimulation was to produce a facilitation of 64 units with a latency of 15 msec or greater and an inhibition of 30 units with a latency of 7 to 10 msec. These two effects were jointly confirmed by computation of post-stimulus time histograms and by conditioning-test procedures employing stimulation of optic tract and midbrain.

Amygdalospinal projections in the cat

Spinal cord injections of rhodamine-labeled fluorescent latex microspheres in the cat resulted in retrograde labeling of a dense, well-defined group of neurons within the central nucleus of the amygdala and a modest number of neurons in the medial nucleus. Amygdalospinal neurons were found to be large cells of variable shape and orientation that were distributed bilaterally with an ipsilateral predominence.

Fluorescent latex microspheres as a retrograde tracer in the peripheral nervous system.

Rhodamine labeled latex microspheres were used as a fluorescent retrograde tracer in the peripheral nervous system. Examination of rabbit trigeminal ganglia following application of microspheres to crushed or intact inferior alveolar nerve revealed that: (1) microspheres were taken up by only damaged axons; (2) microspheres remained in trigeminal cell bodies for up to 3 months without degradation or diffusion to extracellular structures; and (3) cells containing microspheres were capable of regenerating axons as evidenced by the return of evoked sensory action potentials and the retrograde axonal transport of True blue. Thus, fluorescent microspheres may be useful tools for in vivo survival studies of peripheral nervous system regeneration and development.

Responses of cat C1 spinal cord dorsal and ventral horn neurons to noxious and non-noxious stimulation of the head and face.

Previous anatomical studies have shown that trigeminal and cervical afferent nerve fibers project to the upper cervical segments of the spinal cord. To determine the response properties of neurons in the upper cervical spinal cord, we studied the response of C1 dorsal and ventral horn cells to electrical and graded mechanical stimulation of the face, head and neck in anesthetized cats. Neurons were classified as low-threshold-mechanoreceptive (LTM), wide-dynamic-range (WDR), nociceptive-specific (NS) or unresponsive, based on their responsiveness to graded mechanical stimulation. Extracellular single unit recordings were obtained from 118 neurons excited by cervical (24), trigeminal (39) or both cervical and trigeminal (55) stimulation and from 24 neurons unresponsive to peripheral stimulation. Based on neuronal mechanical response properties, 52.2% of the responsive neurons were classified as LTM, 35.9% as WDR and 11.9% as NS. WDR neurons exhibited more convergence and had larger receptive fields than either NS or LTM neurons. WDR and NS neurons had longer first spike latencies than LTM neurons at all tested sites. Only WDR neurons were found to project to the contralateral caudal thalamus. Within C1, LTM neurons were located primarily in laminae III and IV, WDR neurons in lamina V and NS neurons in laminae VII and VIII. These data suggest that some neurons in the first cervical segment of the spinal cord receive convergent input from trigeminal and cervical pathways and may be involved in mediating orofacial and cranial pain.

Pontomedullary raphe neurons: intracellular responses to central and peripheral electrical stimulation

The responses of pontomedullary raphe neurons to electrical stimulation of the medullary reticular formation (MRF) and the mesencephalic ventral periaqueductal gray region (PAG) were studied using intracellular methods in chloralose-anesthetized cats. Single shock stimulation of PAG at the level of the trochelear nucleus evoked short latency, monosynaptic excitatory postsynaptic potentials (EPSPs) in antidromically identified raphe-spinal neurons. Similar large EPSPs were produced by medullary reticular stimulation of either side. The large majority of raphe-spinal neurons responded to sciatic nerve shock, and most responded to tooth pulp or forepaw shock as well; these responses were always bilateral. The responses of cells that could not be antidromically invaded from spinal cord were similar to those of raphe-spinal neurons, but tended to be more variable. Intracellular injection of horseradish peroxidase into electrophysiologically characterized cells revealed that most recordings were made from large and medium sized raphe neurons. These findings are discussed in the context of a potential role for pontomedullary raphe neurons in nociception.

Excitatory projection from the interpeduncular nucleas to central superior raphe neurons

The projection from the interpeduncular nucleus (IP) to the central superior raphe nucleus (CS) was studied using electrophysiologic methods. IP stimulation generates monosynaptic EPSPs in a large number of CS neurons studied with latency of 1-2 ms. Intracellular peroxidase injections into CS neurons responding to IP shock confirmed the location and somatic origin of intracellular potentials. These findings document the existence of a direct excitatory projection from IP onto CS neurons.