Phylogeny, Behavior, and Ontogeny: neural conservation and ...aliceabr/phylogeny_of_brain_anatomy.pdf · significance (telencephalon presents a basic level of organization across

Phylogeny, Behavior, and Ontogeny:neural conservation and adaptation in vertebrates

By Bradly Alicea, NEU 820, Summer 2005

Introduction

Structure of talk (focus on spatial cognition and cognitive maps):

* Conserved Anatomical Mechanisms.

* Conserved Behavioral Mechanisms.

* Evidence of Neural Homology and Monophyly.

* Competing Hypotheses on Cortical Ontogeny and Phylogeny.

* Two "Forces" of Neural Evolution.

Conserved Anatomical Mechanisms:Spatial Behavior (cont'd)

Select spatial orientation mechanisms are conserved in vertebrates:

* vestibular mechanisms and reflexes similar from fishes to Primates.

* superior colliculus – conserved in mammals, cells in this area integrate visual and auditory inputs; use them for orienting organism to stimuli.

* intrinsic and extrinsic connectivity and tectoreticular projectionsare also highly conserved in optic tectum

* may be important for transforming spatial information into a temporal signal among brainstem generators.

Conserved Anatomical Mechanisms: Spatial Behavior (cont'd)

Gene expression data support the conclusions of anatomical and functional studies regarding homology:

* Homeotic genes that help restrict telencephalic zones are highly conserved throughout phylogeny.

* regulatory genes like Dlx-1 and 2 (subpallium), Emx-1 and 2 pallium), and Pax6 (pallial-subpallial boundary) expressed in ontogeny among teleosts and amniotes alike [1].


The is the superior colliculus of the human brain. Note that it provides a basis for both multisensory integration and selective attention.


The hippocampusalso plays a role in spatial behaviors (medial temporal lobe/HC in human brain shown here). Function, but not necessarily the structure, of the hippocampal formation is generally conserved through evolution.

Conserved Anatomical Mechanisms: Spatial Behavior (continued)

Tectal (a.k.a. Superior Colliculular) mechanisms for sensorimotor integration and orientation are well-conserved in vertebrates:

* multisensory integration characteristics [2].

* deep layers correspond to a spatially-ordered motor map, while superficial layers correspond with a retinotopic visual map [3].

* both intrinsic and extrinsic connectivity and the organization of tectoreticular projections (used to map a spatial coordinatesystem to a temporal signal).

Conserved Anatomical Mechanisms:Spatial Behavior (continued)

While conservation of brainstem mechanisms for spatial behaviorhas become widely accepted, the conservation of mechanisms in more anterior parts of the brain have not.

* adaptations to ancestral "bauplan" have minor functional significance (telencephalon presents a basic level of organization across vertebrates.

* despite obvious cytoarchitectural and morphological differences, equivalent pallial and subpallial zones can be identified.

* phylogenetic out-group analysis indicates that the medial, dorsal, and ventral pallial subdivisions are homologous in vertebrates.

Conserved Anatomical Mechanisms:Spatial Behavior (cont'd)

Medial cortex-dependent allocentric spatial learning and memory may have been an trait of amniote common ancestor.

* capacity through the function of generalized structure wasconserved and refined in each subsequent lineage. These additional specializations can either be monophyletic or polyphyletic.

* lateral pallium in actinopterygian fishes is similarly involved in place learning (medial cortex is derived form of pallial structure).

* likewise, lateral pallium lesions in goldfish severely disrupt place learning, but not cue- or egocentric-based strategies [4].

Conserved Behavioral Mechanisms: Spatial Behavior

A "world-centered" mapping of absolute space provides a stable frame in which to carry out movements in space accurately and flexibly:

* hippocampal maps provide a substrate for relational memories,is an non-human mammal equivalent of human declarative and episodic memory.

* a number of behavioral studies show that teleosts and reptiles canalso use cognitive mapping strategies.

* turtles and goldfish can navigate accurately and flexibly to a goal based on an array of landmarks [5].

Conserved Behavioral Mechanisms: Spatial Behavior (continued)

Spatial relations can be encoded by a map-like neuronal representation that provides a stable frame of reference. Two important properties of cognitive (spatial, etc.) maps:

1) they store redundant information so that when spatial cues become unavailable, accurate navigation is still possible is based on those cues that remain.

2) by extension of property #1, they exhibit elements of short-term memory. Turtles and goldfish exhibit no impairment when cues are occluded or removed (no one cue is essential in locating the target).

Conserved Behavioral Mechanisms:Spatial Cognition (cont'd)

Relative volume of medial cortex is is larger in a lizard species that forages actively for prey compared to species with a "sit-and-wait" strategy.

* medial cortex lesions produce severe and selective place memorydeficit in turtles (tested in a dry maze).

* medial cortex lesions in turtles do not impair the use of guidance and other non-relational, egocentric strategies to reach the goal.

* processes that are impaired and not impaired given lesions are highly homologous between medial temporal lobe (mammals) andmedial cortex (reptiles).

Conserved Behavioral Mechanisms:Spatial Cognition (cont'd)

Sex differences in spatial navigation ability may also have an evolutionary basis among mammals and may be rooted in differentialstructure and function of the hippocampus:

* in species where males have larger territories (common among mammals), a general trend is for males to possess keenernavigational and mental rotation abilities [6].

* in these same species, another general trend is for females to possess keener spatial organizational and sorting abilities.

* links between range size and sexual selection strategies may also be important.

Evidence of Neural Homology and Convergent Evolution

Homology = shared derived characteristic, Convergence = trait evolved independently multiple times.

Concepts of homology and convergent evolution (using morphological characters).

Evidence of Neural Homology and Convergent Evolution (cont'd)

Are cognitive mapping capabilities of reptiles and teleosts based on function of pallial structures?

Are they homologous to the hippocampus?

Reptile medial cortex is a homology of the hippocampal formation in mammals [7].


Neural mechanisms for spatial navigation are homologous:

1) function (similarbehavioral strategies).

2) structure (as seen in developmental change).

3) probably emerged in late Paleozoic –early Mesozoic.


In the figure at the left, a weaklyelectric fish brain shows a basal form of the three-lobed vertebrate brain [8]:

* forebrain: olfactory processing.(telencephalon – basal nuclei).

•midbrain: visual processing.(mesencephalon – optic tectum).

•hindbrain: auditory processing.


Modern anatomical studies show Avian brains have a more developed pallium than was previously thought [9].

* pallial and striatal domains of the telencephalon may have all been inherited from fishes.

* conserved but selectivelymodified in each lineage.


Six-layered neocortex of mammals is homologous to Avian hyperpallium, which consists of semi-layered subdivisions [9]:

* nuclear pallial organization (homologous in reptiles and birds) may not be the ancestral condition for mammals (may be an intermediate form of pallial organization).

* behavioral studies have shown that birds perform behaviors such as visual categorization and recall and complex tool use.

* Acetylcholine and dopaminergic terminals found in Mammalian neostriatum (originating in midbrain); in Avians, this type of function is limited to the paleostriatum .

Conservation of Function Across Phylogeny

Actinopterygian (ray-finned) fishes also provide an interesting view of how this lineage-specfic specialization may take place:

* eversion (as opposed to the evagination process in the mammalian lineage) of the neural crest takes place during embryonic development.

* produces a reversal in pallial topography (medial-to-lateralbecomes lateral-to-medial).

* protein synthesis and transcription factor studies have shown that activity in lateral pallium (specifically the nucleolar organizing region – NOR) increases during allocentric navigation.

Conservation of Function Across Phylogeny (cont'd)

Rodriguez et al [11] tested goldfish in a plus-maze in a room with extramaze cues:

* both novel and well-trained start locations were used. Deficits after lateral pallium lesions were similar to those produced by the complete ablation of both telencephalic hemispheres.

* medial or dorsal pallial lesions do not produce deficits in place learning.

* lateral pallium is involved only in place learning; lesions to this area do not impair cue- or other egocentric strategies.

Is It Convergent Evolution or Local Optimality?

See [12] for a recent study that uncovers/confuses the issue.

Phylogeny of Cortical Development

How to build a complex brain:

* in Mammals, there is an increase in cortical sheet size in comparison with the rest of the brain ("encephalization" most apparent in dolphins and Primates.)

* this increased size does not translate into complex morphology,however.

* frugivory, extended life-history, and sociality have been associated with encephalization in Primates, but not so much in other orders [13].

Phylogeny of Cortical Development (cont'd)

Social Brain Hypothesis [14]:

* Dunbar suggests that social group (band) size among Primates can be allometrically scaled to isocortical volume.

* as more social bonds are made and the need for evaluating them increases, so does the size of isocortex.

* Relationship has been found to hold true across the order (including humans).


Morphological changes in brain structures and cortical sheets can have an effect on function. As brains change, a greater heterogeneity in the size of neurons and the thickness of dendrites and axons are seen [15]:

* dendrites and axons must both thicken to maintain its conductance properties. When the number of neurons and glia increase, the proportional connectivity of each neuron with others in it’s functional network often decreases.

* a certain number of neurons are needed to maintain functionality. If the brain grows or shrinks, or connections are added or cut beyond a certain threshold, functions can be lost or gained. Dendrite thickness, dendrite length, and cortical length are all interrelated.


We must also understand developmental mechanisms that give rise to an expanded cortical sheet, since tracking ultimate causes of growth is elusive. How and why does neocortex expand at expense of other telencephalic structures?

1) more cells are generated in development (changes in timing of cell division cycles of progenitor cells in ventricular zone duringneurogenesis).

2) apoptosis (genetically programmed cell death) is decreased during corticogenesis. Knockout mice without Casp9 exhibit a larger proliferative zone in forebrain and larger isocortex size [16].

Competing Hypotheses for Cortical Development

Cortex is trained in ontogeny by spatiotemporal activity of afferents. This requires multiple cues involving regional or gradients of molecules along with signals regulated by afferents [17].

Protomap Hypothesis: there is detailed specification of cortical areas by genes and molecules in a manner that recapitulates cortical parcellation.

Protocortex Hypothesis: cortex is a "tabula rasa" in the sense that its structure is determined solely from thalamic afferents in development.

Competing Hypotheses for Cortical Development (cont'd)

Which is closer to "the truth"?

* cortical maps are often in the same places in the brain (e.g.somatosensory cortex, visual cortex), but their connectivity is itinerant.

* mapping studies of the somatosensory cortex show that use-dependence shapes the topology of the "homunculus".

* after limb deafferentation or sensory ablation (especially during ontogeny), these cortical regions change their representations.

Phylogeny of Cortical Development

Vertebrate sensory cortex evolution according to Krubitzer and Kahn (who use development as a proxy for evolutionary changes inisocortex) [18]:

* certain regions, such as S1, S2, A1, V1, and V2 are ancestral and homologous across vertebrates.

* other areas, such as V5/MT (motion perception) and specialized areas for auditory and visual recognition of conspecifics in primates [19], are specializations that have only arisen in certain lineages.



Adult neurogenesis differs across vertebrates (represents developmental-like growth after traditional “critical-period” window):

* Mammalian neurogenesis is restricted to the hippocampus and olfactory bulbs, whereas birds show more widespread neurogenesis.

* by contrast, reptiles exhibit enormous potential for regeneration and new neuronal incorporation [20].

* lesions of the lizard medial cortex result in intense neuronal birth and migration to damaged areas [21].


Cross-species comparison featuring mouse (Rodentia) and monkey (Primates) pre-natal neurogenesis.

* Notice that length of gestation, length of the critical period, and cell cycle duration are all important andinterrelated variables.

* manipulating cell cycle kinetics can alter patterns of Emx2 and Pax6 [22].


Developmental manipulations may replicate evolutionary differences, especially some surprising morphological changes:

* inject FGF2 into 3rd ventricle; isocortical cells re-enter S-phase (become stem cells again) and grow cortical fields.

* FGF-induced brains can grow additional fissures. However, given same input, no growth in cortical sheet containing V1.

Some things do not change with developmental manipulation; the number of Brodmann's areas correspond with complex behaviors and cannot be constrained during development.

Two "forces" of Brain Evolution

Two interacting forces shape the development of the brain in phylogeny and ontogeny: the expression of gene cascades and activity-dependence.

Two "forces" of Brain Evolution (cont'd)

Comparative analyses suggest that the order of neurogenesis is highly conserved in mammals:

* neural structures produced later in ontogeny (such as isocortex) are disproportionally larger [22].

* disproportionate allocation of isocortex compared to other telencephalic structures due to a shift in regional boundaries of gene expression in embryonic telencephalon.

* Odontoceti, Proboscidea, and Hominoidea have achievedhomoplastic cortical sheet expansion abilities (example of convergent evolution in brain).

Force #1: Genetic Regulation

Several gene cascades act to regulate cortical sheet size:

* beta-catenin: transgenic mice that overexpress a truncated form of this gene produces exaggerated horizontal growth of cortex.

* BF-1/Foxg1: regulate progenitor cell proliferation and differentiation in isocortex of immature mice.

* BF-1 is positively regulated by Fgf8 but negatively regulated by BMP4. Increases in BMP4 expression correlated with decreases in cell proliferation in mouse telencephalon.

* Fgf2 also involved in positively regulating cortical sheet size (cell proliferation and neurogenesis during development).

Force #1: Genetic Regulation (cont'd)Particular genes and proteins serve as signaling centers and mark axes of the cortex (transcription factors act as "postal codes"):

* Shh and Wnt mark the ventral and dorsal telencephalon, respectively (functionally different regions).

* BMP (bone morphogenic protein) may assign the dorsal telencephalon.

* Emx2 and Pax6 are also involved in specifying the anterior-posterior axis of cortex (deletion of these genes causes either a caudal or rostral shift in thalamocortical afferents).

* FGF8 is essential of patterning in the rostral cortex (reductionsof this factor shifts the gradients of several other factors).

Force #1: Genetic Regulation (cont'd)Major subdivisions of the brain (telencephalon, midbrain, hindbrain, and spinal cord) are specified by gradients and other patterns of gene expression:

* homeobox genes Emx1, Emx2, Otx1, and Otx2 are expressed in rostral portions of embryonic brains (exhibit some overlap).

* in diencephalon, Otx1, Otx2, and Wnt3 expression coincidewith anatomical subdivisions.

* single genes or combinations of genes in spatial and temporalcombination of expression strictly control field emergence,organization, architecture, and connectivity.

Force #2: Activity DependenceAssignment of cortical domains, number of cortical fields withina domain, and the organization of a particular cortical field indevelopment are dependent upon activity-dependence generated by particular sensory receptor arrays.

* illustrated by animals with highly specialized morphological features or sensory receptor arrays.

* cortical domain territories assigned to a particular sensory system. (star-nosed mole has a large cortical representation devoted to its nose, while echolocating ghost bat uses large amounts of sensory cortex to represent auditory inputs).

* cortical sheet can be same size, but used differentially.

Force #2: Activity Dependence (cont'd)

In the example at the left [23]:

* significant recruitment of visual cortex by auditory and somatosensory cortex, morphology of visual area changes.

* cross-modal plasticity of sensory cortex demonstrates pluripotentiality (potential to develop multiple functional specializations).

Force #2: Activity Dependence (cont'd)

Comparisons of cortical domain assignment between the duck-billed platypus and star-nosed mole:

* highly specialized phenotypic traits (such as the duck's bill) are overrepresented in the sensorimotor cortex.

* phenotypic trait comes first, then activity, then cortical representation (changes in cortical representation can be induced by the limbdeafferentation within species).

"Forces" and links to phylogenyIn phylogeny, cortical representations are modified in evolutionthrough both intrinsic changes at the molecular level and throughalterations to peripheral morphology and associated use.

* real issue is how specifications of cortical fields are shaped by intrinsic and activity-dependent mechanisms operating togetherduring ontogeny to produce a particular cortical phenotype.

* two features of cortical organization are genetically mediated and highly constrained throughout evolution.

1) position of cortical fields relative to one another is invariant across mammals.

2) thalamocortical connectivity, especially between major sensory nuclei, is also highly conserved.

"Forces" and links to phylogeny (cont'd)

How do alterations occur within lineages?

* all mammals have a constellation of fields present, even in the absence of apparent use (in the somatosensory cortex of the flying fox, some fields are interdigitated with or completely embedded in other fields).

* cortex is relatively homogeneous early in development, cortical fields represent points of ancestral connectivity between the thalamus and cortex [18].

* in phylogeny, these patterns shift due to additions or alterations in peripheral sensory arrays (results in shifting the geographic location of homologous cortical fields and the emergence of new patterns of connectivity (fields).

"Forces" and links to phylogeny (cont'd)The link between ontogeny and phylogeny in the brain is captured in the figure at left.

* four-step interaction modelbetween cortex and thalamus.

* as more thalamic afferents require connections with cortical fields, and cortical fields expand, cortex is realigned to form new architectonic areas.

* common "recruitment" patternsreplicated in heredity?

Future DirectionsLeah Krubitzer claims that “tweaks” in connectivity, morphological

structure, and gene expression patterns can be inhereted:

* Does this follow a set of rules (e.g. “compression” of cortical areas along neuraxis among closely related species)?

* how do developmental “tweaks” transcend the Weismann barrier?

* is there a strong feedback mechanism between the regulation of gene expression, activity-dependence, and behavior?

Sources[1]: Marcus, 2004. The Birth of the Mind: how a tiny number of genes creates the complexity of the human mind.

[2]: Stein and Meredith, 1993. The Merging of the Senses.

[3]: Sparks, 2002. Nature Reviews Neuroscience, 3, 952-964.

[4]: Salas et al, 1996. Brain Behavioral Research, 79, 193-200.

[5]: ----- 1999. Animal Behavior, 57, 51-60; ----- 1999. Animal Cognition, 2, 109-120; ------ 1994. Animal Learning and Behavior, 22, 409-420.

[6]: Gaulin paper.

[7]: based on embryological, cytoarchitectural, connectivity, neurohistochemical, and physiological evidence (----- 1981. Annual Review of Neuroscience, 4, 301-350; Nieuwenhuys et al, 1998. The Central Nervous System of Vertebrates.

[8]: ----- 1998. Albert et al, Evolution, 52(6), 1760-1780.

[9]: --------- 2005. Avian Nomenclature Consortium Nature Neuroscience Reviews, 6, 151-159.

[10]: [9]: Avian Nomenclature Consortium, Nature Reviews Neuroscience, 6, 151-159.

[11]: Rodriguez et al, 2002. Journal of Neuroscience, 22, 2894-2903.

[12]: Sumbre et al, 2006. Current Biology, 16, 767-772.

[13]: Allman, Evolving Brains, 1999.

[14]: Dunbar, Evolutionary Anthropology, 6: 178-190, 1988.

[15]: Kaas, Brain and Mind, 1: 7-23, 2000.

Sources (con’t)[16]: Kuida et al, Cell, 94: 325-337, 1998.

[17]: Sur and Leamey, Nature Reviews Neuroscience, 2: 251-262, 2001.

[18]: Krubitzer and Kahn, 2003. Progress in Neurobiology, 70: 33-52.

[19]: Marc Hauser paper.

[20]: Garcia-Verdugo et al, Brain Research Bulletin, 57(6): 765-75, 2002.

[21]: Molowny et al, Neuroscience, 68(3): 823-36, 1995.

[22]: Bishop et al, 2000.

[22]: Finlay and Darlington, Science, 268: 1578-1584.

[23]: Kahn and Krubitzer, PNAS, 99(17): 11429.

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Phylogeny, Behavior, and Ontogeny: neural conservation and ...aliceabr/phylogeny_of_brain_anatomy.pdf · significance (telencephalon presents a basic level of organization across