4. FUNCTIONAL ROLES OF DENDRITES “D

4. FUNCTIONAL ROLES OF DENDRITES
“Dendrites are the brains of the neurons” and “the spines are their multifunctional units” (Shepherd, 1996). They possess the principal receptors and neural processing complexes (“machines”) of each neuron (Fig. 3.12). Their roles are in part expressed by their characteristic morphological differences in the various regions of the brain and spinal cord. These are features of the diversity and richness of dendritic arborization patterns coupled with the many varieties of spines on their branches (Fig. 2.2). Dendritic spines, each usually not more than 1 μm3 in volume, are diverse in shape and size. However, in vivo imaging observations have demonstrated that spines can form, collapse, reform, and change size and shape rapidly in response to a diverse array of stimuli, and thereby exhibit activity-dependent plasticity (Elhers, 2002).
Of the estimated 1014 synapses on the 1011 neurons in the human cerebral cortex, over 90% are excitatory axo-dendritic synapses. Excitatory glutamate receptors are present primarily on the dendritic spines and inhibitory GABA receptors are mainly on the dendritic shafts, cell body, and the axon’s initial segment. The processing resulting from the stimulation of the ionotropic receptors of the transmission system and the metabotropic receptors of the modulation systems is more complex than that involved in postulated algebraic summation of EPSPs and IPSPs that generates the action potentials of the axon. Some evidence indicates that dendritic synaptic activities are critical in the biochemical mechanisms for regulating the synthesis of synaptic-specific proteins. Some of these proteins are presumably involved in such phenomena as learning and memory (processes by which knowledge of facts, experiences, and skills are acquired and stored).
Dendrites throughout the CNS have roles in processing the neural inputs derived from the sensory receptors. They are integrated and converted into patterns expressed as exquisitely coordinated motor movements. Dendrites contain significant morphologic and functional entities (e.g., spines, postsynaptic densities, and ribosomes) to fulfill their roles within this neurobiologic organization by (1) genetic (genomic) influences and (2) environmental (epigenetic) influences (Chap. 6). The construction of the basic neuronal networks and their synaptic connections are guided by genetically coded rules, followed by the subsequent fine-honing of these connections from responses to the ongoing environmental influences that translate into a variety of neural adjustments such as plasticity (Chaps. 2 and 6). The effectiveness of synaptic transmission, of the modification of existing proteins, of the synthesis of new proteins, and of plasticity are among the neural phenomena occurring in dendrites continuously being modified with changes in activity and experience (Chap. 25).
The major excitatory transmitter released from the presynaptic terminals of synapses in the CNS is the amino acid L-glutamate. This transmitter excites (1) mainly postsynaptic ionotropic glutamate receptors that directly gate ion channels and (2) metabotropic receptors that indirectly gate channels linked to second messengers. Most glutamate receptors are located on the spines and relatively few on the shafts of dendrites. The fact that each dendritic spine usually accommodates a single synapse suggests that the significance of a spine relates to the creation of a local synapse-specific compartment, rather than as a mere expansion of the postsynaptic surface area (Shepherd, 1996). The consensus is that spines function as microcompartments of chemical signals and regulatory proteins that segregate as well as integrate synaptic signals. An increase in the number of compartments can enhance the informational processing power of dendrites. Some evidence indicates that retrograde neural signals from a spine to the presynaptic axon terminal acts to enhance presynaptic function.
The spines have postsynaptic densities (PSDs) that are attached to the cytosolic surface of the postsynaptic membrane (Figs. 3.8 and 3.12). The PSDs are large protein signaling machines (biochemical signaling pathways) with roles (1) in regulating the strength of synaptic transmission (Kennedy, 2000), (2) in modifying spine morphology, and (3) influencing the synthesis of synaptic-specific proteins.
The scaffolding proteins embedded in the PSDs act as linkages for the stimuli from the plasma membrane glutamate receptors (via interaction domains) to the receptors of the smooth endoplasmic reticulum (ER) to receptors of the cytoskeletal actin filaments with their morphogens (types of induction signals) that influence spine shape and size. Each spine has a framework of dense actin filaments, called the spine apparatus, that serves as a (1) support and framework for localizing functional molecules, (2) means for propelling ingredients from the shaft of the dendrite to the PSD and in spine motility (Fig. 3.12), and (3) source of spine morphogens that influence synaptic function during development and plasticity. Powered by actin filaments, the spines exhibit considerable motility.
The DNA of each neuron’s nucleus provides genetically coded information to form messenger RNA (mRNA) that conveys the genetic message through the nuclear pores to the cytoplasm. The mRNAs attached to ribosomes (the genetic message can then be translated into the primary structure of a specific protein by the molecular factories of the ribosomes) migrate via neurotubules (acting like a monorail) to and within the dendritic arbor to locate near the base of and within a spine (Fig. 3.12). Molecular triggers activate mRNAs located within the spine for translation to synaptic-specific proteins. Messengers synthesized at the synapse could be involved in an active feedback with the nucleus of the neuron’s cell body in modulating DNA transcription. The activity level of the synapses may have a role in regulating the formation of mRNAs, the transport of ribosomes on the neurotubules, and the selection of certain ribosomes to localize adjacent to the appropriate base of spines where the mRNA translation to synaptic-specific proteins is sustained and regulated (alternate terms include ribopolysomes or synapse-associated polyribosomes that are mRNAs with added ribosomes engaged in protein production). Biologists traditionally view the nucleus as the command center supplying mRNAs translation into protein. Neurons might have slightly modified this strategy by the synthesis of proteins in spines, and thereby exert influences on synapse-specific protein production in consort with other related synapses. This effect by a synapse might be another factor that enables the nervous system to utilize the neural information received for strengthening specific synapses with fresh proteins for a variety of neuronal activities. It is even possible that certain proteins are uniquely involved in learning and memory. In essence, the functional activities of the synapses, PSD signaling machines, mRNA production, and synapse-specific proteins are
integrated by homeostatic integration with the neuron’s nucleus, by which intraneuronal signaling cytoskeletal pathways from the spine communicate with the nucleus (Fig. 3.12). Indications are that active synapses of the spine have a significant role in the regulation of translation and in the direction of transport of a ribosome to a spine. Although the synapsespecific proteins produced might contribute to learning and memory; the linkage between dendritic protein synthesis and learning and memory, as yet, has not been established. Synapses that undergo long-lasting changes in strength are likely to contribute to learning and memory. Thus, the dendritic spines function as the recipients of (1) neural information via their synapses from both the external environment and from the internal environment of the body and (2) genomic information from the neuron’s nucleus, This is consistent with the role of the spines as multifunctional units of the dendrites as the brains of the neurons. In neurons, gene expression involves a distributed network of translating machines in a functional group of neurons. The polyribosomes are positioned near synapses and translate populations of mRNAs within selected spines. The localization of translation machinery and mRNA at synapses endows individual synapses with the capability of independently controlling synaptic strength through the local synthesis of proteins. The newly synthesized protein presumably has roles in replacing degraded proteins, increasing the levels of existing proteins or even in creating novel proteins.