Richard F. Thompson

Neuronal plasticity in the limbic system during classical conditioning of the rabbit nictitating membrane response: I. The hippocampus.

Hippocampal unit responses were recorded throughout classical conditioning of the rabbit nictitating membrane response to a tone conditioned stimulus (CS) using a corneal air-puff unconditioned stimulus (UCS). Multiple unit analysis revealed that a rapidly developing increase in cell discharges (relative to spontaneous activity) occurs within the first block of paired trials and continues to increment with subsequent training, initially in the UCS period and then in the CS period. The pattern of hippocampal activity within paired trials closely parallels the amplitude-time course of the behavioral response and precedes it temporally. Identical recordsings from animals given unpaired CS-alone and UCS-alone presentations showed no such changes. These control results and additional lines of evidence point to the critical necessity of the learning paradigm for the development of the hippocampal response seen in conditioning animals. A single unit analysis indicates that not all hippocampal neurons exhibit the described conditioned discharge pattern. Hippocampal long-term potentiation is considered as a possible mechanism for mediating this early and rapid neuronal plasticity dependent on specific contingent patterns of stimulation.

The Search for the Engram

Publisher Summary nThis chapter focuses on learning and memory and its neural bases. Learning and memory is a major topic in the field of psychology. Here also, both descriptive mechanical models and formal mathematical models have been developed. In the past, psychologists studying learning have generated a rich data base from behavioral experimentation. For example, much of the research in the Pavlovian conditioning has been designed to determine the ways in which temporal, logical, and qualitative relationships between stimuli (CS and US) influence learning. From this body of empirical knowledge, they have developed very successful models, in the form of sets of abstract learning rules that are able to account for many of the experimental findings. The strength of this approach has been that the theoretical models are able to integrate and deduce a wide range of learning phenomena and make predictions that lead to new experiments. A weakness of this approach, from the perspective of a neurobiologist, is that these psychological models do not make contact with the biological systems that underlie the behavioral phenomena.

Number Coding in Association Cortex of the Cat

In electrophysiological investigations of single neurons in cortical association response areas of the cat, cells have been encountered that appear to code the property of number. In a sequence of stimulus presentations, these cells characteristically discharge to a particular numbered stimulus in the series. This effect is independent of stimulus modality, intensity, and interstimulus interval; thus, the cells seem to be responding to the number of stimulus presentations.

Neuronal plasticity in the limbic system during classical conditioning of the rabbit nictitating membrane response. II: Septum and mammillary bodies

Neuronal unit activity was recorded from several limbic system structures during classical conditioning of the rabbit nictiating membrane response to a tone CS. Air puff to cornea was used as a UCS. The present and past investigations of hippocampal activity using this paradigm show a neuronal plasticity which develops early in training, increases rapidly and shifts forward in time as behavioral conditioning develops. Recordings from the lateral septal region demonstrate the same within-trial pattern of unit discharge seen in hippocampus, indicating a projection of hippocampal plasticity over precommissural fornix pathways. Medial septal neurons, on the other hand, respond in an excitatory manner to the onsets of tone and air puff stimulation. While unit discharges seen in hippocampus and lateral septum occur only during the paired (learning) paradigm, medial septal activity is identical under both paired and unpaired (control) conditions. The latter fact lends support for a sensory interpretation of medial septal responses, and is consistent with anatomical evidence of a major septohippocampal projection originating from this region. In contrast to results for lateral septum, recordings from medial and lateral mammillary nuclei indicate only small, diffuse excitation that exhibits no consistent changes over training, and is not related to activity seen in hippocampal or septal regions. The apparent lack of correspondence between learning dependent unit measures obtained from pre- and postcommissural fornix structures is entirely consistent with current modified descriptions of limbic system anatomy.

Effects of stimulus frequency and intensity on habituation and sensitization in acute spinal cat

Abstract Habituation and sensitization of the flexor withdrawal reflex (tibialis anterior muscle) were studied in acute spinal cat as a function of stimulus intensity and frequency for frequencies ranging above 1 2 sec. The following relationships were consistently observed: (1) habituation is an exponential decline in response amplitude which occurs as a function of iterated stimulation of cutaneous afferents. In some instances habituation may be described as linear over much of its course; (2) habituation occurs more rapidly and to a greater degree of response decrement for higher frequencies of stimulation; (3) habituation is more pronounced for low intensities of stimulation than for high intensities, and; (4) sensitization occurs as a response increment with repetitive stimulation of cutaneous afferents under certain circumstances and may show two distinct time courses, short-term and long-term sensitization. These two phenomena may be differentiated on the basis of stimulus intensity, frequency and their interaction.

Hippocampal unit-behavior correlations during classical conditioning

The correspondence that develops over the course of classical conditioning between the temporal distribution of increased unit activity in the rabbit hippocampus and the amplitude--time distribution of the behavioral nictitating membrane response is analyzed. Results reveal a high degree of correspondence between neural and behavioral measures. The real time correlation between the within-trial probability and increased hippocampal unit discharge and amplitude--time course of the nictitating membrane response grows substantially with learning. Further analyses reveal that this apparent increase in correlation results from a growth in amount of hippocampal unit activity per se (i.e., a differentiation of the hippocampal unit response from background firing rates), rather than an increase in the correspondence between cellular and behavioral measures (i.e. a repatterning of hippocampal discharges to more accurately code spatio-temporal aspects of the behavioral response). These and other results indicate that the neuronal temporal model of the behavioral response either develops within the hippocampus from the first few conditioning trials or develops first in entorhinal cortex to subsequently influence hippocampal discharge patterns. On the other hand, the increase in amount of hippocampal unit activity developing with conditioning appears to occur within the hippocampus.

Diencephalic distributions of ascending reticular systems

Abstract The ascending projections of the brain stem reticular formation were mapped using electrophysiological methods. Low voltage single pulse electrical stimulation of the ponto-mesencephalic reticular core produced short latency unit discharges and evoked responses in two discrete diencephalic regions: the intralaminar-ventral anterior nucleus system and the subthalamus. In the telencephalon, short latency responses were found in the internal capsule and in the head of the caudate nucleus. These results are compared with earlier physiological and anatomical studies on the distribution of ascending reticular projections and the relationship of the findings to the problem of reticular projections to cortical association areas is discussed.

Neuronal plasticity recorded from cat hippocampus during classical conditioning.

It has been demonstrated recently that hippocampal neurons show a very early and marked increase in activity during classical conditioning which continues to grow over the course of training but does not develop in animals given unpaired control trainingl-3,L The preparation used is the rabbit nictitating membrane (NM) response 9, which has several advantages for analysis of brain substrates of learning 7,s,11. Because the conditioned increase in hippocampal unit activity is so large (an average increase of 15-20 standard scores) and consistent 1-3, appears to involve a large proportion of the pyramidal neurons 4, and is projected from the hippocampus to a major efferent target (lateral septum)2, 5, it is at least possible that these findings have tapped an important functional role of the hippocampus in learning and memory. If this is indeed the case, it is necessary to demonstrate generality of the findings across species. A method for classical conditioning of the cat nictitating membrane response under conditions essentially identical to those used for the rabbit has been reported recently ~0. The purpose of the present study is the initial characterization of possible increases in hippocampal unit activity during classical conditioning of the NM response in the cat, using conditions identical to those previously employed with the rabbit. The experiments were performed on 6 cats obtained from local animal pounds. Each animal was anesthetized with pentobarbital (Nembutal) and a multiple unit microelectrode (insulated stainless steel insect pin, size 0) with a 40-50/~m tip exposure implanted into the hippocampus. Electrode placement was determined by stereotaxic coordinates and by monitoring spontaneous unit activity during descent. Histological results showed that all electrode recording sites were in or near pyramidal or dentate granule cell layers. Following a 10-14 day recovery, animals were placed in an experimental enclosure 3,1° consisting of a restraint box and a double-walled, ventilated isolation chamber. The first day of training consisted of adaptation to restraint and the

A Dual-Process Theory of Habituation: Neural Mechanisms

Publisher Summary This chapter discusses neurophysiological evidence from experiments on the flexion reflex of acute spinal cat as well as analyses of other “model” neurophysiological systems which are relevant to the theoretical speculations. This follows the previously discussed dual-process theory of response to repeated stimulation in which two independent processes, one decremental and one incremental, are suggested to account for the behavioral outcome to a series of repetitive stimuli. Data provides evidence for separate and distinct neuronal correlates for the two processes of habituation and sensitization and that suggestive evidence regarding the neuronal substrates of these behavioral processes have come from a wide variety of neurophysiological preparations. The chapter also demonstrates that habituation of the flexion reflex of acute spinal cat is characterized by the same behavioral parameters, which characterizes habituation in intact organisms and suggests further that an analysis of this model mammalian system might provide a key to understanding the neurophysiological mechanisms of response habituation in intact organisms.

Reciprocal anatomical connections between hippocampus and subiculum in the rabbit: Evidence for subicular innervation of regio superior

Anatomical connections between the dorsal hippocampus and subiculum were examined in the rabbit, using horseradish peroxidase (HRP) and autoradiographic methods. A previously undescribed pathway was found to project from the dorsal prosubicular-subicular region to dorsal hippocampal cell fields CA1 and CA2. Autoradiographic findings showed that subicular afferents travel via two routes. One pathway projected through the alveus and stratum oriens, with results suggesting collateral input to the basal dendritic pyramidal cell region. The other projection coursed through the stratum lacunosum-moleculare with apparent termination onto CA1 and CA2 apical dendrites. Regions of subiculum providing afferents to hippocampus were compared with subicular areas receiving efferent terminations from hippocampal CA1 and CA3 cell zones. Distribution of hippocampal-subicular terminations were regionally distinct from subicular retrograde cell fields in rostral areas of the subicular complex, extended over a much wider area of subiculum than was seen for retrograde-labeled cells, and was cytoarchitectonically organized. In total, findings indicated that a reciprocal anatomical relationship exists between dorsal hippocampus and subiculum in the rabbit.