As a result of alternative splicing, the D2 gene of the dopamine receptor family exists in two isoforms. The D2 long is characterized by the insertion of 29 amino acids in the third cytoplasmic loop, which is absent in the short isoform. We have produced subtype-specific antibodies against both the D2 short and D2 long isoforms and found a unique compartmentalization between these two isoforms in the primate brain. The D2 short predominates in the cell bodies and projection axons of the dopaminergic cell groups of the mesencephalon and hypothalamus, whereas the D2 long is more strongly expressed by neurons in the striatum and nucleus accumbens, structures targeted by dopaminergic fibers. These results show that the splice variants of the dopamine D2 receptor are differentially distributed and possess distinct functions. The strategic localization of the D2 short isoform in dopaminergic cell bodies and axons strongly suggests that this isoform is the likely dopamine autoreceptor, whereas the D2 long isoform is primarily a postsynaptic receptor.

Typical neuroleptic drugs elicit their antipsychotic effects mainly by acting as antagonists at dopamine D2 receptors. Much of this activity is thought to occur in the cerebral cortex, where D2 receptors are found largely in inhibitory GABAergic neurons. Here we confirm this localization at the electron microscopic level, but additionally show that a subset of cortical interneurons with low or undetectable expression of D2 receptor isoforms are surrounded by astrocytic processes that strongly express D2 receptors. Ligand binding of isolated astrocyte preparations indicate that cortical astroglia account for approximately one-third of the total D2 receptor binding sites in the cortex, a proportion that we found conserved among rodent, monkey, and human tissues. Further, we show that the D2 receptor-specific agonist, quinpirole, can induce Ca ²⁺ elevation in isolated cortical astrocytes in a pharmacologically reversible manner, thus implicating this receptor in the signaling mechanisms by which astrocytes communicate with each other as well as with neurons. The discovery of D2 receptors in astrocytes with a selective anatomical relationship to interneurons represents a neuron/glia substrate for cortical dopamine action in the adult cerebral cortex and a previously unrecognized site of action for antipsychotic drugs with affinities at the D2 receptor.

Brain stimulation has become one of the most acceptable therapeutic approaches in recent years and a powerful tool in the remedy against neurological diseases. Brain stimulation is achieved through the application of electric currents using non‐invasive as well as invasive techniques. Recent technological advancements have evolved into the development of precise devices with capacity to produce well‐controlled and effective brain stimulation. Currently, most used non‐invasive techniques are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), whereas the most common invasive technique is deep brain stimulation (DBS). In last decade, application of these brain stimulation techniques has not only exploded but also expanded to wide variety of neurological disorders. Therefore, in the current review, we will provide an overview of the potential of both non‐invasive (rTMS and tDCS) and invasive (DBS) brain stimulation techniques in the treatment of such brain diseases.

Modulating Visual Memory: Layer 3 of the secondary visual cortical area V2 plays a role in visual information processing. However, in contrast to layer 3, layer 6 of visual cortex is composed of many types of neurons and their response to visual stimuli is more complex. The importance of layer 6 in visual information processing remains an enigma. López-Aranda et al. (p. 87 ; see the Perspective by Saksida ) investigated its role in the rat visual cortex in the processing of both short- and long-term visual memory. Elimination of neurons from layer 6 of area V2 led to complete loss of normal memory. However, overexpression of a protein called RGS-14 in the same area boosted the visual memory capacity in such a way that the animals retained the visual information for many months, rather than the normal 45 minutes.

Tetrameric AMPA-type ionotropic glutamate receptors are primary transducers of fast excitatory synaptic transmission in the central nervous system, and their properties and abundance at the synaptic surface are crucial determinants of synaptic efficacy in neuronal communication across the brain. The induction of long-term potentiation (LTP) leads to the insertion of GluA1-containing AMPA receptors at the synaptic surface, whereas during long-term depression (LTD), these receptors are internalized into the cytoplasm of the spine. Disruptions in the trafficking of AMPA receptors to and from the synaptic surface attenuate both forms of synaptic plasticity. Homeostatic scaling up and scaling down, which are additional types of plasticity similar to LTP and LTD, are also regulated by the insertion and removal of GluA1-containing AMPA receptors from the synaptic surface. The trafficking of AMPA receptors is an intricate process assisted by various proteins. Furthermore, AMPA receptors are critical for the formation and consolidation of various types of memory, and alterations in their function are intimately associated with cognitive dysfunction in aging and several neurological and psychiatric diseases. In this review, we will provide an overview of the current understanding of how AMPA receptors regulate various forms of synaptic plasticity, their contribution to memory functions, and their role in aging and brain diseases.