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Functional Maps Within A Single Neuron: Review
Functional Maps Within A Single Neuron: Review
A QUESTION THAT HAS BEEN CENTRAL to several defining debates gence of the literature toward viewing dendrites and their ion
in neuroscience is whether neurons and their dendrites are channels as facilitators of the two conjoined goals of efficiently
simple integrate-and-fire units or machines capable of complex encoding incoming local information and maintaining homeo-
computational tasks. A few critical instances where this ques- stasis through this process.
tion has been central are the rate vs. temporal coding debate Functional maps across neurons constitute a common design
(Branco and Hausser 2011; Shadlen and Newsome 1995, 1998; principle in various regions of the central nervous system.
Softky 1995; Softky and Koch 1993), the debate on whether These topographic maps are systematic and continuous spatial
dendritic nonlinearities play a critical role in neuronal infor- representations of information within a brain region, where
mation processing (Chen et al. 2011; Jia et al. 2010; Kitamura adjacent neurons represent adjacent points along a parametric
and Hausser 2011; Losonczy and Magee 2006; Losonczy et al. space (Luo and Flanagan 2007; Schreiner and Winer 2007).
2008; Lovett-Barron et al. 2012) and the origins of extracellu- For example, topographic maps of the visual world exist along
lar field potentials (Buzsaki et al. 2012). The literature presents the primary visual pathway, starting at the retina, through the
a diversity of opinions spanning a large spectrum, including visual thalamus to the primary visual cortex. Similar somato-
those that present extreme standpoints (see references above) topic in primary somatosensory cortex and of tonotopic order
and those that constitute subtle differences in terms of what in primary auditory cortex extend this topographic order to
molecular/cellular processes mediate specific dendritic nonlin- other sensory modalities (Petersen 2007; Schreiner and Winer
earities (Angelo et al. 2007; Hoffman et al. 1997; Magee 1998, 2007). Functional maps of numerous other properties such as
1999; Narayanan and Johnston 2007; Stuart and Sakmann direction selectivity, color, or stereo processing, in the visual
1994; Stuart and Spruston 1998). Here, we present a case for cortex (DeAngelis and Newsome 1999; White and Fitzpatrick
viewing dendritic information processing through the lens of 2007; Xiao et al. 2003) and echo delay and sound source
the sensory map literature and argue for a potential conver- location in bats (Schreiner and Winer 2007) also have been
reported. Apart from these, maps of grid cell spacing (Moser et
Address for reprint requests and other correspondence: R. Narayanan,
al. 2008) and intrinsic oscillatory frequency (Giocomo et al.
Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, 2007) in the entorhinal cortex, maps in the motor cortex
India (e-mail: rishi@mbu.iisc.ernet.in). (Graziano and Aflalo 2007), and olfactory glomerular maps
www.jn.org 0022-3077/12 Copyright © 2012 the American Physiological Society 2343
Review
2344 FUNCTIONAL MAPS WITHIN A SINGLE NEURON
(Luo and Flanagan 2007) have also been reported, establishing intrinsic phase response (Narayanan and Johnston 2008). It
the commonality of this design principle across numerous brain should be noted that different neurons exhibit different map
regions. In this cross-literature review, we extend this map structures for the same parameters, and the set of maps that
metaphor to single neurons and submit our argument that exist within a neuron also depends on the neuronal subtypes.
several functional parameters that are known to possess orderly Numerous recent reviews provide excellent overviews of these
gradients within a single neuron can be investigated from the functional maps from multiple perspectives (Lai and Jan 2006;
perspective of topographic functional maps. Expanding on this Migliore and Shepherd 2002, 2005; Nusser 2011; Sjostrom and
extended metaphor, we present our thesis that explorations into Hausser 2006; Spruston 2008).
this emerging field on intraneuronal maps are bound to benefit What mediates these maps? By our definition (above) of
by drawing direct equivalents from the well-developed litera- functional maps, we suggest that these maps are maintained by
ture on interneuronal sensory maps. Specifically, we present active mechanisms; passive attenuation of voltage signals as a
analogies spanning maps in these two scales in terms of their function of distance (Rall 1977) would thus not be called a
functions, underlying mechanisms, plasticity, activity depen- map. These functional maps are largely maintained by gradi-
dence, and neuromodulation, apart from comparing their com- ents in densities of one or various ion channels within the
putational, developmental, and genetic facets. In this process, topology of the neuron. Whereas gradients in K⫹ channels
we establish straightforward equivalences across these two contribute to a map of bAP amplitude (Hoffman et al. 1997;
Measurement value
and Hausser 2011). Thus, in general, various functional maps synaptic plasticity; in other words, they mediate metaplasticity
within a neuron are critically reflective of various aspects of (Chen et al. 2006; Frick and Johnston 2005; Sjostrom et al.
intraneuronal filtering and/or activity patterns of the network. 2008). Furthermore, because synaptic and intrinsic plasticity
mechanisms can be induced by similar plasticity induction
Plasticity of Intraneuronal Functional Maps protocols (Lujan et al. 2009; Shah et al. 2010; Sjostrom et al.
2008), such metaplasticity would affect intrinsic plasticity
The intraneuronal functional maps are not static entities; mechanisms as well, thus altering various intraneuronal maps,
they are highly dynamic and can undergo either local or global either locally or globally, in an intricately coupled manner.
plasticity. All the major well-characterized map systems men- Several common themes emerge by comparing plasticity in
tioned above have been demonstrated to undergo either local or these intraneuronal maps to plasticity in sensory maps. For
global modulations, depending on the kind of activity patterns. instance, studies involving the effects of dark rearing on
The oldest and most well-established system of plasticity is various visual maps could be metaphorically related to the
that associated with EPSP amplitude. Bidirectional regulation studies involving activity blockade to a neuronal map. In both
of EPSP amplitude has traveled a long distance since the initial cases, the maps respond to changes in the environment by
demonstration of long-term potentiation (LTP) by Bliss and changing their own characteristics. Similar to the case where
Lomo (1973). The biochemical signaling mechanisms involved multiple maps in the visual system respond differently to the
modulators would be dependent on various parameters that through a variety of combinations of conductances (Marder
include intraneuronal gradients in receptor subtypes for spe- and Goaillard 2006). If that is the case, what constrains specific
cific neuromodulators, the properties of channel subtypes, and neuronal classes to exhibit specific intracellular map struc-
the associated signaling mechanism present across various tures? Why cannot another set of map structures replicate the
compartments along the neuron, the volume of neuromodula- same target behavior of the cell? Is it the map structure that
tory projections onto various subregions of the neuron, and the guides the activity levels of the network, or vice versa, or does
state of the neuron during the arrival of neuromodulatory the modulation exist on both ways? Although the answers to
inputs. For instance, different neuromodulatory substances these questions are certainly unknown and are worth rigorous
have been demonstrated to modulate dendritic action potentials exploration, three broad hypotheses come about as possible
along different directions through various pathways (Hoffman answers.
and Johnston 1999; Sjostrom et al. 2008), and the effect of
dopamine on h channels in entorhinal cortical pyramidal neu- Efficient Coding and Intraneuronal Functional Maps
rons is dependent on the state of the neuron and dopamine The first could be considered as an extension of what is
receptor subtype (Rosenkranz and Johnston 2007). Systematic known as the efficient coding hypothesis, which states that a
analyses of the impact of different neuromodulators on maps group of neurons should encode information as compactly as
that span the same neuronal topograph could provide insights possible, to utilize the available resources most effectively.
A Interneuronal maps
B Intraneuronal maps Fig. 2. Efficient coding hypothesis from a cel-
lular neurophysiology perspective. A: from a
systems neuroscience perspective, neurons in
sensory areas efficiently encode natural stimu-
lus statistics corresponding to sensory informa-
Sensory regions Single neuron tion in the external world. B: from a cellular
neurophysiology perspective, compartments
within neurons in different brain regions en-
Network statistics code network statistics that are naturally im-
Natural stimulus statistics
pinging on them, with the network forming the
microenvironment where this neuron resides.
The external world forms the environment The network forms the environment
networks within and across brain regions, similar to what has with either retraction or formation of new synapses and
been postulated with interneuronal maps (Chklovskii and Kou- spines. This postulated synergy between wiring diagrams
lakov 2004). A standard paradigm that has driven neuroscience and intraneuronal maps is thus a rich avenue for further
Development of Intraneuronal Functional Maps role of these intraneuronal maps in regulating intrinsic excit-
ability and dynamics are well established (Kim and Linden
The developmental origins of sensory maps and the influ-
2007; Mozzachiodi and Byrne 2010; Shah et al. 2010), sys-
ence of genetics and environment on their early development
tematic theories relating the two have not emerged.
form central themes in the interneuronal map literature and
have contributed heavily to our understanding of neural plas- Finally, the principle of self-organization where local com-
ticity at the molecular, cellular, and systems levels in the putations lead to the emergence of global order in map forma-
context of the external environment (Chalupa and Rhoades tion, through interactions between adjacent computational el-
1978; de Villers-Sidani et al. 2007; Fregnac and Imbert 1978; ements, has been very useful in understanding neuronal com-
Hirsch and Spinelli 1970; Petersen 2007; Wiesel and Hubel putations and their interactions in sensory maps (Goodhill
1963). What mediates the developmental formation of the 2007; Kohonen and Hari 1999; Swindale 1996). With refer-
intraneuronal maps? What are the relative genetic and envi- ence to intraneuronal maps, we postulate that similar self-
ronmental (network activity) influences on the development of organizing schemes would play a critical role, with the differ-
these intraneuronal maps? Is there an early developmental ence that the global order in terms of the emergence of these
period, a critical period, during which these maps are more functional maps would be consequent to local computations in
plastic? Answers to these questions lie in understanding the dendritic compartments, enabled through interactions between
developmental profile of the ion channel gradients that underlie ion channels present in these compartments. In this context, it
A B
Fig. 3. Non-local influences foster global
Influence across compartments
orderly progression of signaling mechanisms within a neuron under different physiological and pathophysiological condi-
would also constitute a map by our initial definition of a tions. These experiments could provide potential convergence
functional map. It is quite possible that the maps that we have of various lines of investigation including neural coding, den-
described here have their basis in some biochemical signaling dritic information processing, sensory integration, homeosta-
map within the neuron, in terms of expression profiles of, say, sis, wiring optimization, channelopathies, and network pathol-
different kinases and phosphatases. For instance, the mamma- ogy.
lian target of rapamycin (mTOR), a serine/threonine kinase Finally, returning to the question of whether dendritic ion
that controls protein synthesis, plays a critical role in certain channels and their gradients are critical to neural information
forms of synaptic plasticity and in regulating local translation processing, under our postulate on efficient coding, it is evident
of ion channels (Kelleher et al. 2004; Raab-Graham et al. that the answer is dependent on the dendritic subregion under
2006). Similarly, there are numerous examples of enzymes that consideration. In the context of our postulate, dendritic ion
are critically involved in synaptic plasticity also playing a very channels have distinct hues and perform distinct functions
important role in regulating dendritic VGICs (Lujan et al. depending on the statistics of the inputs that they receive at that
2009; Shah et al. 2010; Sjostrom et al. 2008), thus suggestive specific dendritic location. Furthermore, because afferent sta-
of potential coregulation of several maps by underlying bio- tistics cover different behavioral states of the animal, and
chemical signaling gradients. because different ion channel combinations could be coding for
Conclusions
AUTHOR CONTRIBUTIONS
In this review, we argue that a variety of functional maps
R.N. prepared figures; R.N. drafted manuscript; R.N. and D.J. edited and
exist within a single neuron, with each serving a basic function revised manuscript; R.N. and D.J. approved final version of manuscript.
that is potentially reflective of intraneuronal filtering or the
statistics of activity in the network that the neurons reside, or
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