The hippocampus as an olfacto-motor mechanism: were the classical anatomists right after all?
Introduction
In the early 20th century, neuroscientists were in general agreement that the function of the hippocampal formation was strongly related to olfaction. Ramon y Cajal, summarizing the results of his pioneering research in this field in 1917, stated: “Discovering, in the upper part of the olfactory or pyriform lobe of the lissencephalic and gyrencephalic mammals of a special focus, with a singular structure, to which comes an important olfactory pathway and from which emanates the principal pathway of exogenous fibres destined for Ammon's horn. By virtue of this finding, there was established the existence of three sequential olfactory foci: the primary olfactory focus or inferior sphenoidal cortex in which terminate the fibres of the external root of the olfactory bulb; the secondary olfactory focus (which we have called angular or spheno-occipital), in which terminate the fibres originating in the preceding (focus); and the tertiary olfactory focus, represented by Ammon's horn and the fascia dentata, the point of final arborisation of the fibres emanating from the cited angular (focus)” [40, p. 137].
In Ramon y Cajal's time, the dentate gyrus was widely regarded as the receptive part of the hippocampal formation, partly because it was believed to receive an olfactory input and partly because the small size of the dentate granule cells was reminiscent of the small granule cells observed in other sensory or receptive areas in the spinal cord, the medulla, and the neocortex [86, pp. 1419, 1561–1562]. Similarly, the large pyramidal cells of Ammon's horn, resembling as they do, cells “of the type recognised in other places as effectory or motor, strongly suggests that the hippocampus (i.e. Ammon's horn) is primarily an effectory structure” [26, p. 204]. Thus, although it was widely recognized that non-olfactory inputs could also reach the hippocampal formation, there was formerly a widespread consensus that the dentate gyrus and Ammon's horn constituted the afferent and efferent components, respectively, of an olfacto-motor mechanism.
Brodal [26] however, criticized the concept that the hippocampal region had an olfactory function on the grounds that: (a) there was no convincing evidence that olfactory inputs actually reached either the entorhinal cortex or the dentate gyrus–Ammon's horn region, and (b) behavioral experiments showed that olfactory conditioned responses were little affected by surgical destruction of the hippocampal region. These criticisms appear to have had a strong effect on neuroscientific opinion, opening the door to theories that the hippocampal formation is involved in other functions, especially: (a) emotion [115], [140]; (b) memory [120], [156], and (c) a central representation of Euclidean space [137]. Evidence relevant to each of these points of view will be discussed in this review.
Section snippets
The role of the hippocampal formation in olfaction
Recent anatomical studies have confirmed the view that the hippocampal formation receives a strong olfactory input. It is well established that the pyriform cortex receives a heavy input from the olfactory bulb and Ramon y Cajal's finding of projections from the pyriform cortex (Cajal's inferior sphenoidal cortex) to the entorhinal cortex (Cajal's angular or spheno-occipital cortex) has been confirmed by anterograde and retrograde transport methods [69], [110]. Cajal's further discovery that
Electrical activity
The morphology and connections of the Ammon's horn pyramidal cells suggested to the classical anatomists that these cells had an effectory or motoric function analogous to the function of the large pyramidal cells of layer V of the neocortex [26], [86]. Support for this view was provided by the finding that nearly sinusoidal 6–12 Hz RSA (theta rhythm) occurs in the hippocampus in rats and guinea pigs in close correlation with such motor patterns as spontaneous head movements, walking, running,
The role of the hippocampus in learning and memory
Gross destruction of medial temporal lobe structures in humans can produce a severe impairment of subsequent ability to learn (anterograde amnesia) together with a more moderate effect on previously acquired learned behavior (retrograde amnesia). There may also be a preservation of the ability to repeat verbal material (such as a series of digits) for a short period after presentation and a normal ability to learn certain skills such as tracing accurately around a figure visible only in a
Does the hippocampus contain a cognitive map?
O'Keefe [135] and Ranck [144] demonstrated the existence of two main classes of units in the hippocampus of the freely moving rat. One group, the complex spike cells, sometimes generate single action potentials, but at other times they generate short high frequency bursts of action potentials (complex spikes). The second group of cells fire only single spikes but at a higher frequency and with a shorter spike duration than the complex spike cells. Since firing in these cells occurs at a high
The hippocampus and emotion
The theory that intellectual or cognitive processes are associated with the neocortex while emotional processes are associated with the limbic system [115], [140] has enjoyed wide support. Papez [140] suggested that the hippocampus, a key component of the limbic system, was involved in emotion on the basis of the fact that Negri bodies (virus particles) occur abundantly in Ammon's horn pyramidal cells in cases of rabies, a disorder associated with ‘intense emotional, convulsive, and paralytic
Are psychological concepts relevant to brain function?
Attempts to relate one or another aspect of brain structure or function to such concepts as emotion, cognition or memory raise a fundamental question. How do we know that these concepts reflect natural subdivisions of brain function? These psychological concepts did not arise from any kind of scientific investigation: their origin lies in the speculations of the philosophers of ancient Greece, transmitted to us chiefly via the teachings of Aristotle [189]. The findings of ethnopsychology
Acknowledgements
This research was supported by a grant from the Natural Sciences and Engineering Research Council of Canada. I thank Francis Boon for technical assistance; Daniella Chirila for typing; and B.H. Bland, H. Dringenberg, R. Humpartzoomian, R. McLachlan, and I.Q. Whishaw for helpful comments on an earlier draft of the paper. The methods used were approved by the Animal Use Subcommittee of the University of Western Ontario.
References (229)
- et al.
Movement-related potentials within the hippocampal formation of the monkey
Brain Res.
(1987) - et al.
Hippocampal EEG and behaviour in dog. I. Hippocampal EEG correlates of gross motor behaviour
Electroenceph. Clin. Neurophysiol.
(1979) - et al.
Hippocampal EEG and behaviour in dog. II. Hippocampal EEG correlates with elementary motor acts
Electroenceph. Clin. Neurophysiol.
(1979) - et al.
Hippocampal EEG and motor activity in the cat: the role of eye movements and body acceleration
Behav. Brain Res.
(1984) - et al.
Frontal amnesia and the dysexecutive syndrome
Brain Cog.
(1988) - et al.
Two generators of hippocampal theta activity in rabbits
Brain Res.
(1975) - et al.
Diencephalic and hippocampal mechanisms of motor activity in the rat: effects of posterior hypothalamic stimulation on behavior and hippocampal slow wave activity
Brain Res.
(1972) - et al.
Electrical stimulation of the hippocampal formation: behavioral and bioelectrical effects
Brain Res.
(1972) - et al.
Generators and topography of hippocampal theta (RSA) in the anesthetized and freely moving rat
Brain Res.
(1976) - et al.
Cellular basis of hippocampal EEG in the behaving rat
Brain Res. Rev.
(1983)
Testing the NMDA, long-term potentiation, and cholinergic hypotheses of spatial learning
Neurosci. Biobehav. Rev.
Brain temperature- and behavior-related changes in the dentate gyrus field potential during sleep, cold water immersion, radiant heating, and urethane anesthesia
Brain Res.
Beta-frequency (15–35 Hz) electroencephalogram activities elicited by toluene and electrical stimulation in the behaving rat
Neuroscience
Responses of the hippocampus to stimulation of the olfactory bulb and of various nerves in five mammals
Exp. Neurol.
Brain tumors in children and adolescents – II. The neuroanatomy of deficits in working, associative and serial-order memory
Neuropsychologia
Effects of amygdaloid lesions, hippocampal lesions, and buspirone on black–white exploration and food carrying in rats
Behav. Brain Res.
Olfactory functioning in temporal lobectomy patients
Neuropsychologia
Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. Part II. Hippocampal slow waves and theta cell firing during bar pressing and other behaviors
Exp. Neurol.
Behavior during hippocampal microinfusions. II. Muscarinic locomotor activation
Brain Res. Rev.
Behavior during hippocampal microinfusions. III. Lidocaine versus picrotoxin
Brain Res. Rev.
Functional correlates of compensatory collateral sprouting by aminergic and cholinergic afferents in the hippocampal formation
Brain Res.
Phencyclidine-induced rotation and hippocampal modulation of nigrostriatal asymmetry
Brain Res.
An olfactory input to the hippocampus of the cat: field potential analysis
Brain Res.
Effects of colchicine-induced cell loss in the dentate gyrus and Ammon's horn on the olfactory control of feeding in rats
Brain Res.
Odor-induced fast waves in the dentate gyrus depend on a pathway through posterior cerebral cortex: effects of limbic lesions and trimethyltin
Brain Res. Bull.
Components of weasel and fox odors elicit fast wave bursts in the dentate gyrus of rats
Behav. Brain Res.
Descending motor pathways and the spinal motor system: limbic and non-limbic components
Progr. Brain Res.
Some comments on the special cognitive functions claimed for the hippocampus
Cortex
Olfactory identification deficits in patients with focal cerebral excision
Neuropsychologia
Frontolimbic lesions and social behavior in the rat
Physiol. Behav.
Dissociation of the contributions of the prefrontal cortex and the dorsomedial thalamic nucleus to spatially guided behavior in the rat
Behav. Brain Res.
Amnesia after a discrete basal forebrain lesion
J. Neurol. Neurosurg. Psychiat.
Olfactory reactions in the brain of the hedgehog
J. Physiol.
Amnesia after anterior communicating artery aneurysm rupture
Neurology
Mamillary body in the rat: topography and synaptology of projections from the subicular complex, prefrontal cortex, and midbrain tegmentum
J. Comp. Neurol.
Topography and synaptology of mamillary body projections to the mesencephalon and pons in the rat
J. Comp. Neurol.
Neuronal sources of theta rhythm in the entorhinal cortex of the rat. I. Laminar distribution of theta field potentials
Exp. Brain Res.
Neuronal sources of theta rhythm in the entorhinal cortex of the rat: II. Phase relations between unit discharges and theta field potentials
Exp. Brain Res.
Unit analysis of hippocampal population spikes
Exp. Brain Res.
The supraspinal control of mammalian locomotion
J. Physiol. (London)
Hippocampal region
Single-unit analysis of different hippocampal cell types during classical conditioning of rabbit nictitating membrane response
J. Neurophysiol.
Distribution of potentials following stimulation of olfactory bulb in cat
J. Neurophysiol.
Hippocampal electrical activity and behavior
Automated analysis of rhythmicity of physiologically identified hippocampal formation neurons
Exp. Brain Res.
Observations on psychology's past and future
Am. Psychol.
Gamma (40–100 Hz) oscillation in the hippocampus of the behaving rat
J. Neurosci.
The hippocampus and the sense of smell: a review
Brain
Neurological anatomy in relation to clinical medicine
An outline for the analysis of dementia: the memory disorder of Huntington's disease
Neurology
Cited by (74)
Oscillations in the dentate gyrus as a tool for the performance of the hippocampal functions: Healthy and epileptic brain
2023, Progress in Neuro-Psychopharmacology and Biological PsychiatryHuman hippocampal connectivity is stronger in olfaction than other sensory systems
2021, Progress in NeurobiologyCitation Excerpt :Furthermore, activity in olfactory cortical areas, in hippocampus and in some neocortical areas, has been found to oscillate with respiratory rhythms even at rest (Heck et al., 2016; Liu et al., 2017; Lockmann and Tort, 2018; Lockmann et al., 2016; Nguyen Chi et al., 2016; Tort et al., 2018; Yanovsky et al., 2014; Zelano et al., 2016). This suggests that respiratory rhythmicity might impact not only local activity, but also network coherence, perhaps including olfactory-hippocampal networks (Macrides, 1975; Macrides et al., 1982; Vanderwolf, 2001, 1992). In humans, however, respiratory rhythmicity of resting olfactory-hippocampal networks remains unexplored.
Theta Oscillations during Active Sleep Synchronize the Developing Rubro-Hippocampal Sensorimotor Network
2017, Current BiologyCitation Excerpt :Importantly, the RN is functionally connected with many other sensorimotor structures, including the cerebellum [11, 12], sensorimotor cortex [13], and hippocampus [14–16]. Although the hippocampus is most typically associated with spatial memory and navigation [17], it has also long been considered a sensorimotor structure [18, 19]. According to the sensorimotor integration model of hippocampal function, the hippocampus interacts with the RN in a bidirectional manner to enable sensorimotor integration during motor performance [14, 20].
Imaging of Functional and Dysfunctional Episodic Memory
2015, Seminars in Ultrasound, CT and MRIBrief maternal separation affects brain α<inf>1</inf>-adrenoceptors and apoptotic signaling in adult mice
2014, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Notably, CEM-CEL amygdala, where α1-adrenoceptors binding was found significantly reduced, receives olfactory information from cortical amygdala and appears functionally connected with the olfactory bulb (McDonald, 1998). In this view, amygdala and hippocampus are integral components of the olfactory system (Swanson and Petrovich, 1998; Vanderwolf, 2001). Especially during early postnatal period, environmental odors convey crucial information for learning of mother–pup attachment and infant survival (Cheslock et al., 2000).