David H. Cohen

Electrophysiological Identification of a Visual Area in Shark Telencephalon

Optic nerve stimulation in the shark evokes short-latency telencephalic field potentials localized to the ipsilateral, posterior central nucleus. Such a well-defined visual area in elasmobranch telencephalon further challenges classical formulations of forebrain evolution. Moreover, its ipsilateral representation confirms recent evidence for a crossed thalamotelencephalic visual projection.

The Neural Pathways and Informational Flow Mediating a Conditioned Autonomic Response

Despite a long-standing interest in the mechanisms by which nervous systems store and retrieve information, it is rather disappointing that most fundamental questions regarding long-term storage remain unresolved. For many years the unavailability of methods appropriate for investigating the dynamics of neural activity constituted a major barrier in this regard. Consequently, the advent of electrophysiological methods, and microelectrode techniques in particular, generated considerable optimism that changes in neuronal discharge patterns during development of learned behaviors could be specified, and that this would yield important insights into many basic questions regarding the cellular basis of storage. Unfortunately, such optimism has generally been unfounded. For example, we still cannot answer such fundamental questions as whether all neurons are capable of plastic change or if this capacity is restricted to certain morphologically and/or neurochemically specialized neuronal elements. We remain ignorant of the regions of the neuron which undergo plastic change and, of course, the nature of such change. In fact, in vertebrate brain we have yet to implicate conclusively any specific synaptic field in long-term storage.

Development of a vertebrate experimental model for cellular neurophysiologic studies of learning.

General criteria that an experimental model for cellular neurophysiologic studies of learning must satisfy are discussed. It is suggested that defensively-conditioned cardioacceleration in the pigeon provides a preparation with a great deal of potential in this regard. Specific criteria are then established and discussed with reference to this specific preparation. The major emphasis in the paper is upon our approach to developing a suitable vertebrate model, particularly its behavioral requirements and the determination of the neuroanatomical pathways mediating development of the learned response. Experimental results illustrate the approach.

Field potential and single unit analyses of the avian dorsal motor nucleus of the vagus and criteria for identifying vagal cardiac cells of origin

Field potentials evoked by mid-cervical vagal stimulation were systematically mapped in the dorsal motor and solitary nuclei of the pigeon. Since responses varied predictably with microelectrode position, they could be used for localization in the dorsal medulla. By varying stimulus intensity and monitoring the vagal compound action potential, contributions of the different compound action potential waves were then established. Activation of the Bl-wave, which includes cardioinhibitory fiber activity, has its most prominent effect in the intermediate rostrocaudal zone of the dorsal motor nucleus in the region of subnuxleus b. This is where the cells of origin of the vagal cardiac fibers have previously been anatomically localized. Single unit experiments then established that (a) vagal motoneurons with axonal conduction velocities in the cardioinhibitory fiber range (8.0-14.5 m/sec) are primarily localized to the intermediate rostrocaudal zone of the dorsal motor nucleus in the region of subnucleus b, and (b) motoneurons in this zone that conduct at 8.0-14.5 m/sec distribute their axons in the cardiac branches. Furthermore, no error is introduced by identifying such neurons with mid-cervical rather than midthoracic vagal stimulation. Thus, the following criteria establish a neuron as giving rise to a vagal cardioinhibitory fiber: (a) localizing it to the intermediate rostrocaudal zone of the dorsal motor nucleus on the basis of the field potential evoked by mid-cervical vagal stimulation; (b) antidromically activating it with mid-cervical vagal stimulation; and (c) demonstrating that its axon conducts at 8.8-14.5 m/sec.

Electrophysiological and electron microscopic analysis of the vagus nerve of the pigeon, with particular reference to the cardiac innervation

The compound action potential components and their associated fiber contingents were investigated in the pigeon vagus nerve with a view toward identifying the vagal cardioinhibitory fibers. In the cervical vagus, the compound action potential evoked by electrical stimulation included four major components that conducted at 17.0-30.0 (A-wave), 8.0-14.5 (B2-wave) and 0.8-2.0 (C-wave) m/sec. Cardiac slowing was not elicited until activation of the Bl-wave, and the bradycardic response was maximal when this component was maximized. Electron microscopic analysis of the cervical vagus revealed myelinated fibers 1.1-6.8 micron in diameter and unmyelinated fibers 0.3-1.4 micron in diameter. A contingent of myelinated fibers approximately 2-4 micron in diameter apparently generated the Bl-wave, while the prominent unmyelinated fiber contingent (37%) accounted for the C-wave. Analysis of various vagal branches indicated that approximatley 20% of the cervical vagal fibers exit the main trunk between cervical and mid-thoracic levels, but few of these are the larger myelinated fibers greater than 2 micron in diameter. The upper abdominal vagus consists largely of unmyelinated and small myelinated fibers, and consequently the vast majority of larger myelinated fibers found in the cervical vagus exit between mid-thoracic and upper abdominal levels, presumably in the cardiac branches. Direct examination of the cardiac branches confirmed this. Thus, it is concluded that the Bl-wave of the compound action potential is uniquely associated with cardiac slowing, that this component is generated by myelinated fibers ranging from 2 to 4 micron in diameter, and that almost all such fibers are destined for the cardiac branches of the vagus.

Avian sympathetic cardiac fibers and their cells of origin: anatomical and electrophysiological characteristics

The sympathetic cardiac innervation of the pigeon was investigated to describe certain anatomical and physiological properties of the cardiac nerve fibers and their postganglionic cells of origin. The compound action potential of the right cardiac nerve has two major components, one conducting at 2.0-5.6 m/sec with no chronotropic effect on the heart and the other conducting at 0.4-1.0 m/sec with a cardioacceleratory effect. Postganglionic neurons responding antidromically to cardiac nerve stimulation were then studied in ganglion 14 which contains most cells of origin of the cardiac fibers. These neurons have refractory periods of approximately 4 msec, following frequencies of less than 4 HZ, and axons conducting at 0.4-2.0 m/sec; this conduction velocity range corresponds to the slower compound action potential component. Electron microscopy of the cardiac nerve revealed unmyelinated fibers ranging in diameter from 0.2 to 1.2 micrometer and a population of myelinated fibers 1.0-3.6 micrometer in diameter. The unmyelinated fibers account for the slower compound action potential component and are largely postganglionic cardioaccelerator axons. The myelinated fibers account for the faster compound action potential component which has no chronotropic effect and is not reflected in postganglionic antidromic latencies; it is suggested that these myelinated fibers are cardiac sympathetic afferents. This study thus establishes electrophysiological criteria for identifying cardiac postganglionic neurons and describes the anatomical basis of these criteria.

Anatomical and physiological characterization of avian sympathetic cardiac afferents

In the preceding paper6 describing the right sympathetic cardiac nerve of the pigeon we reported a fast compound action potential component with no chronotropic effect, and single unit recordings from sympathetic postganglionic neurons demonstrated that this action potential component was not reflected in the antidromic postganglionic latencies. Electron microscopy then indicated the presence of numerous myelinated fibers in the nerve, and together these findings suggested the existence of a substantial number of sympathetic cardiac afferents in the right cardiac nerve. The present paper confirms this by demonstrating with retrograde transport of horseradish peroxidase that some fibers of the right sympathetic cardiac nerve have their cells of origin in dorsal root ganglia. This was also shown to be the case for the left sympathetic cardiac nerve. Selective activation of the myelinated fiber contingent was then shown to elicit a short latency decrease in arterial blood pressure that could be further augmented by the activation of the smaller unmyelinated fibers. This reflex depressor response to activation of sympathetic cardiac afferents survived bilateral vagotomy but was blocked by atropine. It is therefore concluded that both the left and right sympathetic cardiac nerves of the pigeon contain afferent fibers, both myelinated and unmyelinated, and that the reflex effect of activating these fibers is a sympathetically mediated vasodilation that is atropine-sensitive.

Retinal afferents to the pigeon optic tectum: Discharge characteristics in response to whole field illumination

Responses of pigeon retinotectal afferents to changes in whole field illumination are quantitatively analyzed for 313 units recorded in the stratum opticum. One hundred per cent of these units were responsive in unanesthetized birds and 92.9 percent in urethane anesthetized preparations. Of the responsive units, 92.4 percent (anesthetized) and 100 percent (unanesthetized) gave on-responses whose discharge characteristics showed an orderly relationship to stimulus intensity. Following the on-response, discharge generally ceased during sustained illumination. At stimulus termination off-responses frequently occurred, their probability being a function of stimulus intensity and duration. This probability, as well as specific response characteristics, could be predicted to a large extent from on-response characteristics. Anesthesia and level of background illumination predictably affected these response characteristics quantitatively but did not alter them qualitatively. It is hypothesized that with respect to whole field illumination the pigeons retinotectal afferents constitute a homogeneous population continuously distributed according to threshold for intensity change.

Toward a cardiovascular neurobiology

Abstract Solutions to important basic and clinical problems, once exclusively within the domain of cardiovascular physiology and cardiology, will ultimately require detailed integrative and cellular studies of the brain. This increasing appreciation of the role of the nervous system in cardiovascular disease is stimulating the development of a ‘cardiovascular neurobiology’.

Effect of avian basal forebrain lesions, including septum, on heart rate conditioning

The possible involvement of basal telencephalic structures in visually conditioned heart rate change (established by pairing light and foot-shock) was studied in 156 pigeons by evaluating conditioning performance following lesions of the septum or lobus parolfactorius. Extensive destruction of the septal complex had no effect on either the orienting response or the development of the conditioned response. Lesions of the lobus parolfactorius did not affect the orienting response or overall conditioned response levels, but it did slightly prolong the latency of the conditioned heart rate change. It is concluded that the septum, despite its being cardioactive, is not involved in conditioned heart rate change and that the lobus parolfactorius participates minimally. Thus, of the principal limbic structures of the avian telencephalon, only the amygdalar homologue appears critical in this defensive conditioning task [3].