Memory (Mechanisms Other than LTP)


Synaptic plasticity is not the exclusive mode of memory storage, and persistent regulation of voltage‐gated ionic channels also participates in information storage. Long‐term changes in neuronal excitability have been reported in several brain areas following learning. Synaptic activation of glutamate receptors initiates long‐lasting modification in neuronal excitability at the pre‐ or postsynaptic side, that is, in the axon, soma and dendrites of central neurons. Intrinsic plasticity is expressed in virtually all neuronal types including principal cells and interneurons. It is mediated by changes in the expression level or biophysical properties of voltage‐gated ion channels in the membrane and can affect many different neuronal operations such as dendritic integration and action potential generation and propagation. Similarly to synaptic plasticity, long‐lasting intrinsic plasticity is bidirectional and expresses a certain level of input or cell specificity. Synaptic and intrinsic plasticities not only share common learning rules and induction pathways but also contribute in synergy with these synaptic changes to the formation of a coherent mnesic engram.

Key Concepts:

  • Synaptic plasticity is a major mode of memory storage.

  • Persistent regulation of voltage‐gated ionic channels also participates in information storage following learning.

  • Synaptic activation of glutamate receptors initiates long‐lasting modification in neuronal excitability at the pre‐ or postsynaptic side.

  • Intrinsic plasticity is mediated by changes in the expression level or biophysical properties of voltage‐gated ion channels in the membrane.

  • Intrinsic plasticity can affect many different neuronal operations such as dendritic integration, action potential generation, action potential shape, action potential propagation and backpropagation.

  • Synaptic and intrinsic plasticities share common learning rules and induction pathways.

  • Synaptic and intrinsic plasticities contribute in synergy to the formation of a coherent mnesic engram.

Keywords: E–S potentiation; LTP; dendrites; synaptic integration

Figure 1.

Facilitation of the input–output function through the regulation of postsynaptic receptors or voltage‐gated channels. (a) Persistent potentiation of synaptic transmission is characterised by enhanced postsynaptic current (EPSC). At the initial segment, the excitatory postsynaptic potential (EPSP) is large enough to cross the action potential (AP) threshold and to elicit a postsynaptic spike. (b) The same result is obtained if the AP threshold is hyperpolarized through the regulation of voltage‐gated channels located at the cell body and/or axon initial segment. Note that here the synaptic current remains unchanged. (c) Enhanced amplification of the EPSP by voltage‐gated channels located in the dendrite allows the generation of a postsynaptic AP without change in the EPSC.

Figure 2.

Local and global changes in intrinsic neuronal excitability. (a) Regulation of ion channels in the dendrites (blue dots) will preserve input specific changes. (b) Modulation of ion channels in the axon (blue dots) will globally affect the excitability of all inputs.



Abraham W, Gustafsson B and Wigström H (1987) Long‐term potentiation involves enhanced synaptic excitation relative to synaptic inhibition in guinea‐pig hippocampus. Journal of Physiology 394: 367–380.

Aizenman CD and Linden DJ (2000) Rapid, synaptically driven increases in the intrinsic excitability of cerebellar deep nuclear neurons. Nature Neuroscience 3: 109–111.

Alkon DL (1984) Calcium‐mediated reduction of ionic currents: a biophysical memory trace. Science 226: 1037–1045.

Alle H and Geiger JRP (2006) Combined analog and action potential coding in hippocampal mossy fibers. Science 311: 1290–1293.

Armano S, Rossi P, Taglietti V and D'Angelo E (2000) Long‐term potentiation of intrinsic excitability at the mossy fiber‐granule cell synapse of rat cerebellum. Journal of Neuroscience 20: 5208–5216.

Asztely F and Gustafsson B (1994) Dissociation between long‐term potentiation and associated changes in field EPSP waveform in the hippocampal CA1 region: an in vitro study in guinea‐pig brain slices. Hippocampus 4: 148–156.

Belmeguenai A, Hosy E, Bengtsson et al. (2010) Intrinsic plasticity complements long‐term potentiation in parallel fiber input gain control in cerebellar Purkinje cells. Journal of Neuroscience 30: 13630–13643.

Beraneck M, Hachemaoui M, Idoux E et al. (2003) Long‐term plasticity of ipsilateral medial vestibular nucleus neurons after unilateral labyrinthectomy. Journal of Neurophysiology 90: 184–203.

Bliss TVP and Lømo T (1973) Long‐lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforent path. Journal of Physiology 232: 331–356.

Brembs B, Lorenzetti FD, Reyes FD, Baxter DA and Byrne JH (2002) Operant reward learning in Aplysia: neuronal correlates and mechanisms. Science 296: 1706–1709.

Burrell BD, Sahley CL and Muller KJ (2001) Non‐associative learning and serotonin induce similar bi‐directional changes in excitability of a neuron critical for learning in the medicinal leech. Journal of Neuroscience 21: 1401–1412.

Campanac E, Daoudal G, Ankri N and Debanne D (2008) Downregulation of dendritic Ih in CA1 pyramidal neurons after LTP. Journal of Neuroscience 28: 8635–8643.

Campanac E and Debanne D (2008) Spike timing‐dependent plasticity: a learning rule for dendritic integration in rat CA1 pyramidal neurons. Journal of Physiology 586: 779–793.

Campanac E, Gasselin C, Baude A et al. (2013) Enhanced intrinsic excitability in basket cells maintains excitatory‐inhibitory balance in hiipocampal circuits. Neuron 77: 712–722.

Cleary LJ, Lee WL and Byrne JH (1998) Cellular correlates of long‐term sensitization in Aplysia. Journal of Neuroscience 18: 5988–5998.

Coulter DA, LoTurco JJ, Kubota M et al. (1989) Classical conditioning reduces amplitude and duration of calcium‐dependent after‐hyperpolarization in rabbit hippocampal pyramidal cells. Journal of Neurophysiology 61: 971–981.

Cowan TM and Siegel RW (1986) Drosophila mutations that alter ionic conduction disrupt acquisition and retention of a conditioned odor avoidance response. Journal of Neurogenetics 3: 187–201.

Cudmore RH, Fronzaroli‐Molinieres L, Giraud P and Debanne D (2010) Spike‐time precision and network synchrony are controlled by the homeostatic regulation of the D‐type potassium current. Journal of Neuroscience 30: 12885–12895.

Daoudal G, Hanada Y and Debanne D (2002) Bi‐directional plasticity of EPSP‐spike coupling in CA1 hippocampal pyramidal neurons. Proceedings of the National Academy of Sciences of the USA 99: 14512–14517.

Debanne D (2004) Information processing in the axon. Nature Reviews. Neuroscience 5: 304–316.

Disterhoft JF, Coulter DA and Alkon DL (1986) Conditioning‐specific membrane changes of rabbit hippocampal neurons measured in vitro. Proceedings of the National Academy of Sciences of the USA 83: 2733–2737.

Egorov AV, Hamam BN, Fransen E, Hasselmo ME and Alonso A (2002) Graded persistent activity in entorhinal cortex neurons. Nature 420: 173–178.

Frick A, Magee J and Johnston D (2004) LTP is accompanied by an enhanced local excitability of pyramidal neuron dendrites. Nature Neuroscience 7: 126–135.

Ganguly K, Kiss L and Poo MM (2000) Enhancement of presynaptic neuronal excitability by correlated presynaptic and postsynaptic spiking. Nature Neuroscience 3: 1018–1026.

Griffith LC, Wang J, Zhong Y, Wu CF and Greenspan RJ (1994) Calcium/calmodulin‐dependent protein kinase II and potassium channel subunit eag similarly affect plasticity in Drosophila. Proceedings of the National Academy of Sciences of the USA 91: 10044–10048.

Hengen KB, Lambo ME, Van Hooser SD, Katz DB and Turrigiano GG (2013) Firing rate homeostasis in visual cortex of freely moving behaving rodents. Neuron 80: 335–342.

Kim J, Jung SC, Clemens AM, Petralia RS and Hoffman DA (2007) Regulation of dendritic excitability by activity‐dependent trafficking of the A‐type K+ channel subunit Kv4.2 in hippocampal neurons. Neuron 54: 933–947.

Kuba H, Oichi Y and Ohmori H (2010) Presynaptic activity regulates Na+ channel distribution at the axon initial segment. Nature 465: 1075–1078.

Li CY, Lu JT, Wu P, Duan SM and Poo MM (2004) Bidirectional modification of presynaptic excitability accompanying spike timing‐dependent synaptic plasticity. Neuron 41: 257–268.

Mahon S and Charpier S (2012) Bidirectional plasticity of intrinsic excitability controls sensory inputs efficacy in layer 5 barrel cortex neurons in vivo. Journal of Neuroscience 32: 11377–11389.

Malik R and Chattarji S (2012) Enhanced intrinsic excitability and EPSP‐spike coupling accompany enriched environment‐induced facilitation of LTP in hippocampal CA1 pyramidal neurons. Journal of Neurophysiology 107: 1366–1378.

Mellor J, Nicoll RA and Schmitz D (2002) Mediation of hippocampal mossy fiber long‐term potentiation by presynaptic Ih channels. Science 295: 143–147.

Misonou H, Mohapatra DP, Park EW et al. (2004) Regulation of ion channel localization and phosphorylation by neuronal activity. Nature Neuroscience 7: 711–718.

Moore SJ, Cooper DC and Spruston N (2009) Plasticity of burst firing induced by synergistic activation of metabotropic gluatamate and acetylcholine receptors. Neuron 61: 287–300.

Moyer JR, Thompson LT and Disterhoft JF (1996) Trace eyeblink conditioning increases CA1 excitability in a transient and learning‐specific manner. Journal of Neuroscience 16: 5536–5546.

Mozzachiodi R, Lorenzetti FD, Baxter DA and Byrne JH (2008) Changes in neuronal excitability serve as a mechanism of long‐term memory for operant conditioning. Nature Neuroscience 11: 1146–1148.

Naudé J, Paz JT, Berry H and Delord B (2012) A theory of rate coding control by intrinsic plasticity effects. PloS Computational Biology 8: e1002349.

Oh MM, Kuo AG, Wu WW, Sametsky EA and Disterhoft JF (2003) Watermaze learning enhances excitability of CA1 pyramidal neurons. Journal of Neurophysiology 90: 2171–2179.

Quirk MC, Blum KI and Wilson MA (2001) Experience‐dependent changes in extracellular spike amplitude may reflect regulation of dendritic action‐potential back‐propagation in rat hippocampal pyramidal cells. Journal of Neuroscience 21: 240–248.

Rosenkranz JA and Grace AL (2002) Dopamine‐mediated modulation of odour‐evoked amygdala potentials during pavlovian conditioning. Nature 417: 282–287.

Ross ST and Soltesz I (2001) Long-term plasticity in interneurons of the dentate gyrus. Proceedings of the National Academy of Sciences of the USA 98: 8874–8879.

Saar D, Grossman Y and Barkai E (1998) Reduced after‐hyperpolarization in rat piriform cortex pyramidal neurons is associated with increased learning capability during operant conditioning. European Journal of Neuroscience 10: 1518–1523.

Santini E, Quirck GJ and Porter JT (2008) Fear conditioning and extinction differentially modify the intrinsic excitability of infralimbic neurons. Journal of Neuroscience 28: 4028–4036.

Scholz KP and Byrne JH (1987) Long‐term sensitization in Aplysia: biophysical correlates in tail sensory neurons. Science 235: 685–687.

Schreurs BG, Tomsic D, Gusev PA and Alkon DL (1997) Dendritic excitability microzones and occluded long‐term depression after classical conditioning of the rabbit's nictitating membrane response. Journal of Neurophysiology 77: 86–92.

Sheffield ME, Best TK, Mensh BD, Kath WL and Spruston N (2011) Slow integration leads to persistent action potential firing in distal axons of coupled interneurons. Nature Neuroscience 14: 200–207.

Walmsley B, Berntson A, Leao RN and Fyffe REW (2006) Activity‐dependent regulation of synaptic strength and neuronal excitability in central auditory pathways. Journal of Physiology 572: 313–321.

Wang Z, Xu NI, Wu CP, Duan S and Poo MM (2003) Bidirectional changes in spatial dendritic integration accompanying long‐term synaptic modifications. Neuron 37: 463–472.

Woody CD and Black‐Cleworth P (1973) Differences in excitability of cortical neurons as a function of motor projection in conditioned cats. Journal of Neurophysiology 36: 1104–1116.

Further Reading

Abraham WC (2008) Metaplasticity: tuning synapses and networks for plasticity. Nature Reviews Neuroscience 9: 387–399.

Beck H and Yaari Y (2008) Plasticity of intrinsic neuronal properties in CNS disorders. Nature Reviews Neuroscience 357–369.

Ganguly K and Poo MM (2013) Activity‐dependent neural plasticity from bench to bedside. Neuron 80: 729–741.

Guzman‐Karlsson MC, Meadows JP, Gavin CF, Hablitz JJ and Sweatt (2014) Transcriptional and epigenetic regulation of Hebbian and non‐Hebbian plasticity. Neuropharmacology 80: 3–17.

Kim SJ and Linden DJ (2007) Ubiquitous plasticity and memory storage. Neuron 56: 582–592.

Mozzachiodi R and Byrne JH (2009) More than synaptic plasticity: role of nonsynaptic plasticity in learning and memory. Trends in Neuroscience 33: 17–26.

Shah MM, Hammond RS and Hoffman DA (2010) Dendritic ion channel trafficking and plasticity. Trends in Neuroscience 33: 307–316.

Sjöström PJ, Rancz EA, Roth A and Häusser M (2008) Dendritic excitability and synaptic plasticity. Physiological Reviews 88: 769–840.

Zhang W and Linden DJ (2003) The other side of the engram: experience‐driven changes in neuronal intrinsic excitability. Nature Reviews Neuroscience 4: 885–900.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Debanne, Dominique, and Campanac, Emilie(Aug 2014) Memory (Mechanisms Other than LTP). In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0021398.pub2]