Apical dendrite
An apical dendrite is a
Background
Two types of dendrites present on pyramidal cells are apical and
Apical dendrites are studied in many ways. In cellular analysis, the electrical properties of the dendrite are studied using stimulus responses. A single surface shock of the cerebral cortex induces a 10–20 ms negative potential, a manifestation of the summed excitatory post-synaptic potentials (EPSPs) evoked in the distal portions of the apical dendrite.[6] This has been called the Dendritic Potential (DP). This is identical with Adrian's Superficial Response in direct cortical responses.[6] At higher intensities the DP is followed by slow positive waves (Adrian's Deep Response) or by a prolonged negative wave lasting for more than 200 ms (Chang’s second component).[6] The highest amplitude of DPs is found on the cortical surface, with the polarity shifted from negative to positive within the superficial layer.[6]
Areas of interest
Hippocampus
The hippocampus contains pyramidal neurons in three areas: CA1, CA2, and CA3.
The stratum oriens is the location between layers containing basal dendrites.[8] The stratum lucidum, stratum radiatum, and the stratum moleculare-lacunosum are layers of apical dendrites and are ordered from least distant to most distant from the soma of the neuron.[8]
Pyramidal cells in CA3
CA3 projects
Hippocampal CA3 pyramidal cells have complex dendritic arbors which receive a stratified pattern of synaptic input from a variety of sources, including:
- the commissural/associational fibers from ipsi- and contra-lateral CA3 pyramidal neurons which synapse on both the basal and mid-apical dendrites in the stratum oriens and stratum radiatum [4]
- the mossy fibers from the granule cells of the dentate gyrus which synapse on the most proximal apical region, the stratum lucidum[4]
- the preforant path fibers from the entorhinal cortical pyramidal cells which synapse in the region of the most distal apical dendrites, the stratum lacunosum-moleculare.[4]
Distal apical dendrites extend upwards from the soma. The shorter proximal apical dendrites extend outward and below. Shape of majority of 2d section is approximately a cylinder with a pointed base for the apical arbor.
In CA3 neurons the inputs are stratified and run in bands parallel to the cell body layer.[4] Dendritic attenuation of synaptic current is described by an exponential relationship. The closer to the body the dendrite, the higher the EPSP amplitude.[4] Electrical measurements and predictions validate the cylinder cross-section model.[4] In the CA3, the temporoammonic (TA), commissural (COM), associational (ASSOC), and mossy fiber (MF) afferents all make excitatory glutamatergic (Glu) synapses on pyramidal cell dendrites (both apical and basal).[2]
Since fast signals occurring in the basilar and proximal apical dendrites are transferred to the soma with at least a 20–25% efficiency, synapses in these dendrites each contribute more to the neuronal activation than distal apical synapses.[4] In contrast, only slow signals from the distal dendrites are efficiently transferred to the soma, suggesting a modulatory role on the resting potential of the cell.[4] It is hypothesized in several studies that this could be accomplished by varying the overall frequency of synaptic activity in the distal apical dendrite.[4] Since a constant barrage of synaptic activity would approximate a constant current injection, the overall level of synaptic activity in the distal apical dendrite could set the depolarization level of the entire neuron.[4] When a more efficient proximal synaptic activity is superimposed upon a sub-threshold depolarization due to distal activity, the cell has a high probability of firing an AP.[4] In CA3, it is the perforant path projection from the entorhinal cortical cells that provides synaptic input to the most distal dendrites of the pyramidal cells. Assuming a frequency average of 7 spikes/sec, as few as five randomly firing entorhinal cortical cells would cause a steady level of depolarization in the distal dendrites of CA3b pyramidal cells.[4] Amplitude and kinetics of the electrical signal vary as a function of position within the dendrite and signal frequency.[4]
The major trigger for CA3 discharge is the afferent input from the
Interneurons in CA3
These are similar to
For the input to the hippocampus proper, the temporoammonic pathway arises in layer III cells of the entorhinal cortex but separates from the perforant pathway to contact the most distal branches of the pyramidal cells in the stratum lacunosum-moleculare of CA1-CA3.[2] The excitatory (glutaminergic) influence of this path has been questioned because influence on the pyramidal cells has been difficult to demonstrate.[2] Recent experiments show that this modulation of pyramidal cells may differentially activate an interneuron subpopulation located in the distal reaches of the apical dendrites.[2]
The study of inhibitory transmission is limited in the pyramidal neurons and their modulators because the large number of excitatory synapses has overshadowed physiological studies of the inhibitory neurons.[9] The structure of inhibitory synapses on apical dendrites may not be as plastic as the excitatory synapses on these neurons.[9] There is difficulty in differentiating the excitatory and inhibitory synapses using the electrophysiological recordings in many experiments.[9] The excitatory synapses and their patterns are by comparison to the inhibitory system rather uniform in type and properties.[9] The inhibitory system, by contrast, possess several (10) different types of synapses originating from specifically differentiated cells and are much more difficult to track.[9] There is insufficient information to precisely distinguish between excitatory and inhibitory pathways contributing to the alterations in neurotransmitter expression and cell structure changes.[9]
CA1
CA1 pyramidal cells make up a homogeneous population which together with relatives in subiculum comprise the primary output cells of the hippocampal formation.
Imaging studies following localized changes intracellular calcium from discrete synaptic inputs have shown a role for these currents in synaptic plasticity.[2] There is disagreement, however, as to how activity-dependent changes in synaptic inhibition might occur.[2] Studies do agree that plasticity is enhanced when inhibition is reduced.[2]
CA2
CA2 differs from other regions because it is one of the few areas to survive
Entorhinal cortex
The
Piriform cortex
In the piriform cortex, layer I consists mostly of afferent inputs to apical dendrites of deeper cells. Layer I is subdivided into layers Ia and Ib each having its own afferents. Layer II is densely packed with pyramidal and semilunar cells. Layer III contains mostly pyramidal cells in its superficial part.[2]
In the piriform cortex the distal apical dendrites of layer III pyramidal neurons receive extrinsic inputs, which the corresponding proximal dendrites receive intrinsic inputs.[5]
Olfactory bulb
In each glomerulus the axons of the receptor neurons contact the apical dendrites of mitral cells, which are the principal projection neurons in the
Cerebral cortex
General
The most superficial layer of the cortex is the molecular or plexiform layer.
Some of the apical dendrites from the pyramidal cells in the cerebral cortex may be up to 10μm in diameter.[11] The apical dendrite of a large pyramidal neuron in the cerebral cortex may contain thousands of spines.[11] Spines in the cerebral cortex vary in size by several orders of magnitude from one region to another. Smallest have a length of 0.2μm and a volume of about 0.04 cubic micrometres and the largest a length of 6.5μm and a volume of 2 cubic micrometres.[11]
Neocortex
Pyramidal cells are the majority class of cells in the neocortex.[2] They have high density of dendritic spines, prominent apical dendrites, and axons that project out of the cortex as well as locally within it.[2] Soma for these appear in all layers except I.[2] Spiny stellate cells are distinguished from pyramidal cells here by the absence of the apical dendrite and the fact that their axons also do not leave the cortex.[2] These cells are thought to begin as pyramidal neurons and then retract their apical dendrites and axons.[2]
Cerebellum
A defining characteristic of Purkinje cells in the cerebellum is the apical dendrite.[10]
Development
Dendritic arbor formation for pyramidal neurons in the cortices occurs progressively beginning in late embryonic stages of development and extending well into post-natal periods.[2] Many dendrites of pyramidal neurons in deep layers branch and form connections in layer IV, while some extend to more superficial layers. Pyramidal cell dendrites in layer III branch to form arbors in layer I. Thalamocortical afferents will make synaptic contact with dendrites in layer IV while myriad of other inputs will meet dendrites in layer I. The post-synaptic structure is driven in part by signals from incoming afferent fibers and through life there is plasticity in the synapses.[2]
The formation of these arbors is regulated by the strength of local signals during development.
Useful models of dendritic arbor formation are the Xenopus tadpoles, which are transparent in early stages of larval development and allow for dye-labeled neurons to be repeatedly imaged in the intact animal over several weeks.[3] It has been observed from this and other models that there are rapid dendritic branch additions and retractions which lengthen the overall dendrite and accumulate more branches. This mirrors the development of axonal branches (both have a lifetime of approximately 10min).[3] This activity decreases as neurons mature. Signals including glutamate from axon branches may increase branch additions.[3]
Within the Xenopus tadpole model, several signaling systems have been studied. For example, in optical tectal neurons, dendrite arbor growth occurs approximately at the onset of retinal input.
Among the signals studied in this system is
- Branches with NMDA-only receptors mature and recruit AMPARs, which stabilize the branches.[3]
- These stable branches then add new branches with NMDAR-only synapses which either stabilize through AMPARs or retract. AMPAR additions are present in adults and account for synaptic plasticity.[3]
- CaMKII strengthening of signals results from the selective trafficking of GluR1 AMPARs into synapses. In long term depression (LTD) the GluR subunits of AMPARs undergo endocytosis.[3]
Temporal differences in signaling over the course of neuron maturation suggest that the most promising studies of arbor development and synaptogenesis in the future are going to occur in intact brain systems.[3]
Another model studied in apical dendrite development is the
However, animal models may be insufficient to elucidate the complexity of these systems. Pyramidal cells in CA1, for example, are 30 times as thick in humans as they are in rats.[14] The entorhinal cortex is also subdivided into as few as 8 and as many as 27 sections in humans (depending on the system used), whereas there are only 2 in rats and 7 in monkeys.[14] The connections of the dentate gyrus and entorhinal cortex are also more sophisticated in humans.[14] In rats and cats, a very large reciprocal connection exists between the entorhinal cortex and the olfactory system.[2] In primates this connection is absent and there are highly differentiated connections between the multimodal parasensory and paralimbic cortices and the EC which are not as evident in rats and cats.[2] The increased size of the primate subiculum may proportionally enhance its effects on the entorhinal cortex.[2]
Sexual dimorphism
Pyramidal cell dendritic arbor formation in the anterior cingulate cortex (layers 2/3) is more complex in males and, in contrast the orbital prefrontal regions, dendritic arborization is greater in females suggesting a fundamental difference in the prefrontal organization in males and females.[15] In rats, for example, exposure to estrogen either exogenously or endogenously during proestrous leads to increases in CA1 spine densities.[10][15] These differences may be due to the presence of gonadal hormones which have been demonstrated to influence cell structure in the hippocampus. Treatment with testosterone has been shown to affect cortical neuron structure.[15]
Pathology
Stress response and PTSD
Dendritic spines, post-synaptic structures receiving mainly excitatory input, are sensitive to experiences in development including stress episodes or drugs. Studies have shown that prenatal stress reduces complexity, length, and spine frequency of layer II/III pyramidal apical dendrites in rat and primate models. Dendritic atrophy has been described in hippocampal formation and prefrontal cortex in both models.[15]
Chronic stress has been shown to reduce the arbor complexity and total dendritic length of apical dendrite trees of CA3 pyramidal neurons in the hippocampus as well.
The prefrontal cortex is also a target for the glucocorticoids in stress ([3H]dexamethasone binds to receptors in frontal and prefrontal cortex at about 75% of concentration of hippocampus).[5] Endogenous regulation of corticosteroid receptors is indicated by altered binding of the previously mentioned compound in the prefrontal cortex with administration of corticosteroids.[5] Furthermore, regulation of stress activities involves the prefrontal cortex. Lesions in rat prefrontal cortices impair spontaneous alternation, radial maze performance, and passive avoidance.[5] In primates these impair inhibition of line-of-sight responses.[5] Chronic administration of corticosteroids decreases 5-HT1A receptor binding, 5-HT2 receptor binding, serotonin levels, and expression of neural cell adhesion molecule (a cell-surface macromolecule involved in regulating aspects of synapse stabilization).[5] These changes indicate structural change follows stress hormone elevation.
Studies of dendritic morphological changes indicate that elevation of stress hormones in layer II-III of the prefrontal cortex causes no observable change in the structure or distribution of basal dendrites.[5] The apical dendrites, however, show a significant redistribution in stress-hormone treated animal brains, which is measured using Scholl analysis.[5] Scholl analysis estimates the amount and distributions of dendrite material by counting numbers of intersections of dendrites with an overlay of concentric rings centered at the soma.[5] Medial prefrontal cortex layer II-III pyramidal neurons showed significant reorganization with a 21% increase in proximal apical dendrite arbors and a decrease of 58% in distal apical dendrite arbors.[5] These results are in contrast to the changes in the hippocampal CA3 dendritic arbors, in which only regressive changes were observed.[5] One possible explanation proposed in these studies is that the atrophy of distal dendrites in II-III layer pyramidal neurons results directly from the loss of input from changed CA3 pyramidal neurons, as both CA1 and CA3 project directly into the medial prefrontal cortex.[5]
It has been determined from electrophysiological data that excitatory synapses on proximal apical dendrites of prefrontal cortex pyramidal neurons serve to amplify excitatory post-synaptic potential (EPSP) signals generated in distal apical dendrites.[5] This suggests that reduction in distal dendrite mass due to the stress hormone elevation may result in an increase in proximal apical dendrite complexity as the proximal apical dendrites attempt to offset the reduced distal apical dendrite signals.[5]
Serotonergic alterations and alterations in glutamate release in the prefrontal cortex indicate that the neurochemical mechanisms altering structure in both the hippocampus and prefrontal cortex are similar.[5]
The division of management between extrinsic and intrinsic inputs to the dendrites in the piriform cortex (mentioned above) is also seen to a lesser degree in the
In studies of hierarchical animals, it was observed that the dominant and subordinate animals show the same degree of dendritic reorganization, indicating that the dendritic atrophy with stress is not degree-dependent.[16]
Metabolic disease
In neurometabolic diseases, distended storage neurons are markedly swollen and pear shaped, with the nucleus and the nissl bodies displaced toward the apical dendrites.[18] Examples of neuron metabolic storage diseases are the sphingolipid storage diseases which typically involve malfunctioning hydrolases in the lysosomes responsible for the degradation of these lipids:
- type 2 and type 3 Gaucher disease[19]
- GM1 gangliosidosis and GM2 gangliosidosis[19]
This swelling is shown, for instance, in Tay–Sachs disease, a GM2 accumulation due to defective beta-hexosaminidase.[19] Visible in this disorder are large mega-neurite formations.[19]
Epilepsy
Cellular mechanisms
It has been indicated that there is a "chicken and egg" issue in the study of models relating to epilepsy because on the one hand the models are used to study the genesis of epilepsy and on the other they are used to study changes in prolonged events.[9] The question arises, therefore, of whether the resulting data of the models indicated an exaggerated defect responsible for the genesis of seizures or whether the data indicated systemic changes to normal tissue after prolonged seizure activity.[9]
Calcium currents, normally prominent in CA1 hippocampal neurons are increased in response to status epilepticus. There is evidence that current in T-type calcium channels is increased specifically in apical dendrites. The hypothesis is that this phenomenon creates a situation in which fast sodium spikes in the soma back-propagate into the dendrites, whereby they detonate bursting.[20]
Dendritic potentials (DPs) also undergo changes. Elicitation of DPs during seizure activity showed that they were much smaller than controls.[6] However, DPs elicited just after seizure termination lasted for longer periods, indicating that suppression of the DP is correlated with the seizure activity itself.[6]
Plasticity in CA1 pyramidal cells and interneurons has been related to CA1 roles in epileptogenesis.[2] CA1 is hyperexcitable when the CA3 region is damaged. Reduction of both GABAA and GABAB IPSPs occurs. GABA interneurons, though intact, become less easily activated.[2]
Seizure input from the EC to the dentate gyrus is filtered for both
Hyperventilation leads to a marked surface negative direct current shift due to depolarization of the apical dendritic trees of the cortical pyramidal cells.[2] This shift is likely to represent the increased excitability of the cortical neuronal networks and may explain the resultant potential epileptogenicity.[2] Certain anti-epileptic drugs have the opposing effect of reducing surface negativity in normal controls.[2]
Temporal lobe epilepsy
Changes in expression of potassium channels and of potassium currents have been described in a model of temporal lobe epilepsy. In this model, there is
Infantile seizures and associated memory impairment
Neuronal death does not appear to contribute to the learning deficits in rats with
Schizophrenia
In individuals with
Human neocortical heterotopia
Heterotopia is the displacement of any organ or component thereof from its natural position.[2] Rat models of telencephalic internal structural heterotopia are used as a model for human neocortical heterotopia.[2] In these models, the apical dendrites of the pyramidal neurons are not consistently radially oriented and may even be inverted.[2] Additionally, the dendrites near the edge of the heterotopic region often bend and follow the contour of the band.[2]
Methods of studying effects
The following list is adapted from Lothman, et al.[8]
In-vivo imaging
- Magnetic resonance imaging (MRI)
- Computerized tomography (CT)
- Positron emission tomography (PET)
- Film autoradiography
- Single photon emission computerized tomography (SPECT)
- Surface, subdural, and depth electroencephalography
- Magnetoencephalography
- Evoked potentials
- Focal electrical stimulation
- Afterdischarges
- Physiological, psychological responses to stimulation
- Single unit recording
In-vitro physiology
- Slices
- In-vitro imaging: standard light and electron microscopy
- Histochemistry
- Immunocytochemistry
- Receptor autoradiography
- Lesions
- Destructive
- Reversible
- Cryolesions
- Pharmacological
Seizure changes
Two methods are studying the relationship between seizures and dendritic impairment:
- Seizures activate stress mechanisms including the excitatory neuropeptide corticotropin-releasing hormone (CRH) from hippocampal neurons.[2] CRH has been shown to interfere with dendritic growth and differentiation.[2] Mice lacking this receptor possess exuberant dendritic trees.[2] However, pyramidal cells exposed to CRH during the first week of life had atrophied dendrites. These stress-related changes reduced synaptic plasticity and caused learning and memory deficits later in life.[2] As antagonists for CRH exist, there exists a potential to reverse or prevent these effects through pharmacological means.[2]
- Studies of recurrent
Optical monitoring
Recording the activity of a single neuron at any given time at many locations in the dendritic tree has been accomplished using voltage-sensitive dyes with optical monitoring.[2] Signals are rapid but also small, and measurements from single cells require intense illumination.[2] As the dyes are very phototoxic, the cells usually die after only a few action potentials.[2] However, measurements from both somatic and dendritic patch recordings show that the peak membrane potential deflection during a paroxysmal depolarizing shift (PDS) is 10mV greater in the apical trunk (supragranular location) than the soma.[2] This is consistent with the anatomy of neocortical networks because the most powerful reciprocal layer connections are in supragranular layers 2 and 3.[2] This may resolve the conflicting information suggesting that the activity spreads primarily at the supragranular layers or at the large layer 5 neurons.[2]
Conventional studies with
Electroencephalogram
Electroencephalogram (EEG) scalp signals are summed EPSPs and IPSPs of nerve cells.[23] EEG can only measure the potentials of cells arranged in organized layers and whose apical dendrites are oriented perpendicularly to the surface of the cortex (as they are in pyramidal cells).[23] The potential measured by the EEG is the difference between the basal and apical parts of the active neurons that are oriented in such a way.[23] The EPSPs that converge on the pyramidal neurons through direct afferent fibers ending in the upper part of the apical dendrites cause a flow of charged ions (a current) between points at different potentials within and outside neurons.[23] The positive ions then enter the cell following concentration and electrical charge gradient and propagate to the rest of the neuron.[23] EPSPs from the distal apical dendrites create a current starting from the apical part nearest to the synapse (where the magnitude is greater) toward the cell body because the resistance to this flow is less.[23] The current perpendicular (or radial) to the apical dendrite is accompanied by a magnetic field that propagates orthogonally (or tangentially) to the current along the extracellular side of the cell membrane.[23] This set of ionic and electrical functional alterations thus generates the fields of electromagnetic potentials or electromagnetic dipoles.[23] These can be defined also as single equivalent dipoles.[23]
References
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- ^ a b c d e f g h i j k l m n o p q r s t u v w x y z aa ab ac ad ae af ag ah ai aj ak al am an ao ap aq ar as at au av aw ax ay az ba bb bc bd be bf bg bh bi bj bk bl bm bn bo bp bq br bs bt bu bv bw bx by Jerome Engel TAP, ed. Epilepsy: A Comprehensive Textbook in Three Volumes. Philadelphia, PA: Lippincott Williams & Wilkins; 2008
- ^ a b c d e f g h i j k l m n o p Cline HT. Dendritic arbor development and synaptogenesis. Current Opinion in Neurobiology 2001; 11: 118–126
- ^ a b c d e f g h i j k l m n o p q r s t u v Henze DA CW, Barrioneuvo G. Dendritic Morphology and its effects on the amplitude and rise-time of synaptic signals in hippocampal CA3 pyramidal cells. Journal of Comparative Neurology. 1996;369:331–344.
- ^ a b c d e f g h i j k l m n o p q r s t u CL W. Dendritic Reorganization in Pyramidal Neurons in Medial Prefrontal Cortex after Chronic Corticosterone Administration. Journal of Neurobiology. 2001;49:245–253.
- ^ a b c d e f Jibiki I MK, Ohtani T, et al. Dendritic Potential in Direct Cortical Responses and Seizure Activity. Folia Psychiatrica et Neurologica. 1978;32(3):329–337
- ^ Bradshaw KD EN, Bliss TVP. SHORT COMMUNICATION: A role for dendritic protein synthesis in hippocampal late LTP. European Journal of Neuroscience. 2003;18:3150–3152
- ^ a b c d Lothman EW BE, and Stringer JL. Functional Anatomy of Hippocampal Seizures. Progress in Neurobiology. 1991;37:1–82.
- ^ a b c d e f g h Mathews, Gregory. Telephone Interview.11/19/08.
- ^ a b c d e f Dale Purves GJA, David Fitzpatrick, William C. Hall, Anthony-Samuel LaMantia, James O. McNamara, and S. Mark Williams, eds. Neuroscience: Third Edition. Sunderland, MA: Sinauer Associates, Inc.; 2004
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- ^ Bender RA BA, and Baram TZ. Neuronal Activity Influences the sub-cellular distribution of hyperpolarization-activated cation channels in hippocampal neurons. Epilepsia. 2005;46(supplement 8):92
- ^ Groc L PZ, Gustafsson B, et al. In vivo blockade of neural activity alters dendritic development of neonatal CA1 pyramidal cells. European Journal of Neuroscience. 2002;16:1931–1938.
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- ^ a b c d Murmu MS SS, Biala Y, et al. Changes of spine density and dendritic complexity in the prefrontal cortex in offspring of mothers exposed to stress during pregnancy. European Journal of Neuroscience. 2006;24:1477–1487.
- ^ a b McKittrick CR MA, Blanchard DC, et al. Chronic Social Stress Reduces Dendritic arbors in CA3 of Hippocampus and Decreases Binding to Serotonin Transporter Sites. Synapse. 2000;36:85-942006;24:1477-1487.
- ^ a b c d e Reith MEA, ed. Cerebral Signal Transduction: From First to Fourth Messengers. Totowa, NJ: Humana Press, Inc.; 2000.
- ^ Haberland C. Clinical Neuropathology: Text and Color Atlas. New York, NY: Demos Medical Publishing, LLC; 2007.
- ^ a b c d Buccoliero A BJ, and Futerman AH. The role of sphingolipids in neuronal development: lessons from models of sphingolipid storage diseases. Neurochemical Research. 2002;27(7/8):565-574
- ^ Dudek FE RM. Current opinions in clinical science: calcium currents burst back: a possible role for dendrites in eliptogenesis. Epilepsy Currents. 2007;7(5):140–141.
- ^ a b c d e Benes FM TM, and Kostoulakos P. GluR5,6,7 Subunit Immunoreactivity on Apical Pyramidal Cell Dendrites in Hippocampus of Schizophrenics and Manic Depressives. Hippocampus. 2001;11:482–491.
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