Correlations between electrophysiological observations of synaptic plasticity modifications and behavioral performance in mammals

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Abstract

Within the past century it has been well established that most mature neurons lose their ability to divide. Since then, it has been assumed that behavioral performance leads to synaptic changes in the brain. The existence of these potential changes has been demonstrated in numerous experiments, and different mechanisms contributing to synaptic plasticity have been discovered. Many structures involved in different types of learning have now been identified.

This article reviews the different methods used with mammals to detect electrophysiological modifications in synaptic plasticity following behavior.

Evidence of long-term potentiation and long-term depression has been found in the hippocampus and cerebellum, respectively, and empirical data has been used to correlate these mechanisms with specific learning performance. Similar observations were made recently in the septum and amygdala. These phenomena seem to be involved in maintaining the performance in the cortical areas of the brain.

Ongoing attempts to find the relationship between behavioral performance and modifications in synaptic efficacy allow to speculate upon the dynamics of cellular mechanisms that contribute to the ability of mammals to modify wide neuronal networks in the brain during their life.

Introduction

behavioral performance can be considered as the result of a behavioral change following one or more events that occur during an animal's lifetime. Changes in behavioral performance can be observed during the information acquisition process that constitutes learning, while the persistence of this change after the learning has been completed is referred to as the memory of that acquisition. In fact, memory is the usual consequence of learning [in Squire (1986)].

Biologists believe that behavioral performance is the result of a more general phenomenon: neuronal plasticity. Reflection on the neurobiological basis needed to retain new information in memory led most early authors to consider some type of growth or change in the existing structure of the nervous system. William James (1890)wrote “the only impressions that can be made upon them [brain and spinal cord] are through the blood, on the one hand, and through the sensory nerve-root on the other…The currents once in must find a way out. In getting out they leave their traces in the paths which they take. The only thing they can do, in short, is to deepen old paths or to make new ones” [in Squire (1986)]. Since then, it has been established that most mature neurons have lost their capacity to divide. The hypothesis that activated nerve cells can grow therefore appeared to be a reasonable way of accounting for the persistence of memory. Such a concept was first introduced by Ramon y Cajal, 1894, Ramon y Cajal, 1911and independently by two of his contemporaries (Tanzi, 1893; Lugaro, 1900). This basic idea has been restated many times since then, and has given rise to the hypothesis that the synapse is the critical site of plastic change (Konorski, 1948; Hebb, 1949; Eccles, 1953).

Advances in neurobiology have produced significant and relevant physiological discoveries since synaptic change was first proposed to explain behavioral performance.

It is now well known that neurons show many kinds of plasticity. Application of electrical stimulation has been shown to produce various synaptic changes: presynaptic changes in the economics of transmitter release (depression, facilitation and post-tetanic potentiation), post-synaptic changes in receptor sensitivity, and morphological alterations in synaptic structure. These results demonstrate that neurons can change in a functionally significant way, and they provide possibilities concerning the actual processes that occur during behavioral learning.

However, there are many steps between synaptic change and behavioral performance. The main purpose of this review is to report experiments that attempted to find correlations between physiological synaptic change and behavioral performance.

Section snippets

Synaptic change: from theoretical to experimental observations

In his now-classic book “The Organization of behavior” (1949), Donald Hebb proposed that memories are stored in the mammalian brain as stronger synaptic connections between neurons that are active during learning. The specific mechanism he suggested to bring about these changes in synaptic transmission is relatively simple. Hebb postulated that increments in synaptic efficacy occur during learning when firing of one neuron repeatedly produces firing in another neuron to which it is connected.

In search of synaptic changes subsequent to behavior

Since clinical observations of the famous `HM' case (Scoville and Milner, 1957), physiological studies aimed at understanding behavioral performance have focused on the hippocampus in animals. The discovery of the mechanism of synaptic plasticity in the hippocampus by Bliss and Gardner-Medwin (1973)and Bliss and Lomo (1973)gave new impetus to the search for correlations between behavioral performance and synaptic change in the nervous system. One of the first attempts was to observe changes in

In aging rats

In an early report (Barnes, 1979), aging rats (28–34 months) were first tested on a spatial task and exhibited poorer memory for the rewarded place in comparison to mature adult rats (10–16 months). When granule cell synaptic responses were recorded after a single session of very brief high-frequency stimulation, the amount of elevation and the time course of the decline were equivalent across age groups. After three repetitions, however, the young rats maintained the increased synaptic strength

In the septum

Regarding synaptic efficacy, it has been postulated, for instance, that spatial information might be stored in the hippocampus as a specific distribution of the weight of modifiable synapses (McNaughton and Morris, 1987). Nevertheless, it may be questioned whether other brain structures that exhibit artificial synaptic change might also play a role in behavioral performance. This is true of the lateral septum (LS), which is considered as an important relay station connecting the limbic

In the cerebellum and related structures

Long-term depression in the cerebellar cortex is a widely studied form of synaptic plasticity in the mammalian brain [for a review, see Ito (1989)]. LTD can be induced either by pairing low-frequency activity in parallel fibers (PFs) and climbing fibers (CFs), two excitatory afferent pathways that converge on cerebellar cortical Purkinje cells (Ito, 1989), or by pairing PF activity with direct Purkinje cell hyperpolarization (Crepel and Jaillard, 1991). The timing of PF and CF stimulation is

Concluding remarks

These observations as a whole indicate that behavioral performance is associated with significant alteration in synaptic efficacy. Thus, since Hebb's original concept of a modifiable cell assembly, experimental designs in mammals have made it possible to observe how these assemblies are modified in a behavioral context. However, there is still a gap between separate observations of synaptic efficacy, whether in vitro in slice preparations or in chronic animals, and performance observed on

References (175)

  • S.A. Deadwyler et al.

    Activity of dentate granule cells during learning: differentiation of perforant path input

    Brain Res.

    (1979)
  • V. Doyère et al.

    Long-term potentiation of hippocampal afferents and efferents to prefrontal cortex: implications for associative learning

    Neuropsychologia

    (1993)
  • H. Eichenbaum et al.

    Odor-guided learning and memory in rats: is it “special”?

    TINS

    (1993)
  • M. Glickstein

    The cerebellum and motor learning

    Curr. Opin. Neurobiol.

    (1992)
  • B. Hars et al.

    Improvement of learning by cueing during postlearning paradoxical sleep

    Behav. Brain Res.

    (1985)
  • T.M. Jay et al.

    Selectivity of the hippocampal projection to the prelimbic area of the prefrontal cortex in the rat

    Brain Res.

    (1989)
  • E.D. Kanter et al.

    NMDA-dependent induction of long-term potentiation in afferent and association fiber systems of piriform cortex in vitro

    Brain Res.

    (1990)
  • S. Laroche et al.

    Post-trial reticular facilitation of associative changes in multiunit activity: comparison between dentate gyrus and entorhinal cortex

    Behav. Brain Res.

    (1983)
  • S. Laroche et al.

    Increase in [3H]glutamate release from slices of dentate gyrus and hippocampus following classical conditioning in the rat

    Behav. Brain Res.

    (1987)
  • S. Laroche et al.

    Linear relation between the magnitude of long-term potentiation in the dentate gyrus and associative learning in the rat. A demonstration using commissural inhibition and local infusion of an N-methyl-d-aspartate receptor antagonist

    Neuroscience

    (1989)
  • S. Laroche et al.

    Long-term potentiation in the prefrontal cortex following stimulation of the hippocampal CA1/subicular region

    Neurosci. Lett.

    (1990)
  • K.S. Lee

    Sustained enhancement of evoked potentials following brief, high-frequency stimulation of the cerebral cortex in vitro

    Brain Res.

    (1982)
  • D.J. Linden et al.

    A long-term depression of AMPA currents in cultured cerebellar Purkinje neurons

    Neurons

    (1991)
  • G. Lynch et al.

    A cortical system for studying cortical memory

    TINS

    (1993)
  • S. Maren et al.

    Properties and mechanisms of long-term synaptic plasticity in the mammalian brain: relationships to learning and memory

    Neurobiol. Learn. Mem.

    (1995)
  • D.A. McCormick et al.

    Lesions of the inferior olivary complex cause extinction of the classically conditioned eyeblink response

    Brain Res.

    (1985)
  • B.L. McNaughton et al.

    Hippocampal synaptic enhancement and information storage within a distributed memory system

    Trends Neurosci.

    (1987)
  • M. Mishkin et al.

    Stimulus recognition

    Curr. Opin. Neurobiol.

    (1994)
  • A.M. Mouly et al.

    On the ability of rats to discriminate between microstimulations of the olfactory bulb in different locations

    Behav. Brain Res.

    (1985)
  • G.I. Allen et al.

    Cerebrocerebellar communication systems

    Physiol. Rev.

    (1974)
  • P. Andersen et al.

    Unit analysis of hippocampal population spike

    Exp. Brain Res.

    (1971)
  • V.A. Aroniadou et al.

    Mechanisms of LTP induction in rat motor cortex in vitro

    Cereb. Cortex

    (1995)
  • A. Artola et al.

    Long-term potentiation and NMDA receptors in rat visual cortex

    Nature

    (1987)
  • H. Asanuma et al.

    Neurobiological basis of motor learning and memory

    Concepts Neurosci.

    (1991)
  • H. Asanuma et al.

    Characteristics of projections from the nucleus ventralis lateralis to the motor cortex in the cats: an anatomical and physiological study

    Exp. Brain Res.

    (1974)
  • A. Baranyi et al.

    Conditioned changes of synaptic transmission in the motor cortex of the cat

    Exp. Brain Res.

    (1978)
  • N.H. Barmack et al.

    Effects of microlesions of dorsal cap of inferior olive of rabbits on optokinetic and vestibuloocular reflexes

    J. Neurophysiol.

    (1980)
  • C.A. Barnes

    Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat

    J. Comp. Physiol. Psych.

    (1979)
  • T.W. Berger

    Long-term potentiation of hippocampal synaptic transmission affects rate of behavioral learning

    Science

    (1984)
  • T.W. Berger et al.

    Limbic system interrelations: functional division among hippocampal–septal connection

    Science

    (1977)
  • T.W. Berger et al.

    Neuronal substrate of classical conditioning in the hippocampus

    Science

    (1976)
  • O.E. Bergis et al.

    Enhancement of long-term potentiation in the dentate gyrus 2 days after associative learning in the rat

    Neurosci. Res. Commun.

    (1990)
  • L.J. Bindman et al.

    NMDA-receptors participate in the maintenance of long-term potentiation of synaptic transmission in slices of rat neocortex in vitro

    J. Physiol. (Lond.)

    (1988)
  • Bindman, L. J., Christofi, G., Murphy, K. and Nowicky, A. (1991) A long-term potentiation (LTP) and depression (LTD) in...
  • T.V.P. Bliss et al.

    A synaptic model of memory: long-term potentiation in hippocampus

    Nature

    (1993)
  • T.V.P. Bliss et al.

    Long-lasting potentiation of synaptic transmission in the dentate area of the unanesthetized rabbit following stimulation of the perforant path

    J. Physiol. (London)

    (1973)
  • T.V.P. Bliss et al.

    Long-lasting potentiation of synaptic transmission in the dentate area of the anesthetized rabbit following stimulation of the perforant path

    J. Physiol. (London)

    (1973)
  • Bloch, V. and Laroche, S. (1984) Facts and hypotheses related to the search for the engram. In: Neurobiology of...
  • V. Bloch et al.

    Enhancement of long-term potentiation in the rat dentate gyrus by post-trial stimulation of the reticular formation

    J. Physiol. (Lond.)

    (1985)
  • C.A. Castro et al.

    Recovery of spatial learning deficits after decay of electrically induced synaptic enhancement in the hippocampus

    Nature

    (1989)
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