Γ-Aminobutyric acid in adult brain: an update.

This review assesses the parallel literature on the role of gamma - aminobutyric acid (GABA) in brain plasticity and GABA elements dysfunction related disorders. I review historical and new data from both animal and human sources which have helped define the key role for this transmitter synthesis, release and reuptake, GABA receptors subtype regulation, and GABAergic neurons function in the adult brain. The role of GABAergic elements in neurological and psychiatric disorders is briefly discussed.

CB1 Cannabinoid Receptor Expression in the Barrel Field Region Is Associated with Mouse Learning.

We found previously that fear conditioning by combined stimulation of a row B facial vibrissae (conditioned stimulus, CS) with a tail shock (unconditioned stimulus, UCS) leads to expansion of the cortical representation of the "trained" row, labeled with 2-deoxyglucose (2DG), in the layer IIIb/IV of the adult mouse the primary somatosensory cortex (S1) 24 h later. We have observed that these learning-dependent plastic changes are manifested by increased expression of somatostatin, cholecystokinin (SST+, CCK+) but not parvalbumin (PV+) immunopositive interneurons We have expanded this research and quantified a numerical value of CB1-expressing and PV-expressing GABAergic axon terminals (CB1+ and PV+ immunopositive puncta) that innervate different segments of postsynaptic cells in the barrel hollows of S1 cortex. We used 3D microscopy to identify the CB+ and PV+ puncta in the barrel cortex "trained" and the control hemispheres CS+UCS group and in controls: Pseudoconditioned, CS-only, UCS-only, and naive animals.

Neurochemical correlates of functional plasticity in the mature cortex of the brain of rodents.

It is commonly accepted that increase of input to sensory structures in mammals is known to produce marked changes in cortical recipient areas. This paper reviews the data concerning manifestations of changes in primary somatosensory cortex of adult animals caused by classical conditioning with reinforcement: aversive (whisker-shock) and appetitive (whisker-water) trainings. These include: anatomical, electrophysiological responses, receptor autoradiography, expression of GABA, GAD at mRNA and protein levels, expression of neuronal and astroglial GAT-1 puncta and inhibitory synaptogenesis in the hollows of "trained" barrels of the adult mouse.

Effect of Associative Learning on Memory Spine Formation in Mouse Barrel Cortex.

Associative fear learning, in which stimulation of whiskers is paired with mild electric shock to the tail, modifies the barrel cortex, the functional representation of sensory receptors involved in the conditioning, by inducing formation of new inhibitory synapses on single-synapse spines of the cognate barrel hollows and thus producing double-synapse spines. In the barrel cortex of conditioned, pseudoconditioned, and untreated mice, we analyzed the number and morphological features of dendritic spines at various maturation and stability levels: sER-free spines, spines containing smooth endoplasmic reticulum (sER), and spines containing spine apparatus. Using stereological analysis of serial sections examined by transmission electron microscopy, we found that the density of double-synapse spines containing spine apparatus was significantly increased in the conditioned mice.

Increases in the numerical density of GAT-1 positive puncta in the barrel cortex of adult mice after fear conditioning.

Three days of fear conditioning that combines tactile stimulation of a row of facial vibrissae (conditioned stimulus, CS) with a tail shock (unconditioned stimulus, UCS) expands the representation of "trained" vibrissae, which can be demonstrated by labeling with 2-deoxyglucose in layer IV of the barrel cortex. We have also shown that functional reorganization of the primary somatosensory cortex (S1) increases GABAergic markers in the hollows of "trained" barrels of the adult mouse. This study investigated how whisker-shock conditioning (CS+UCS) affected the expression of puncta of a high-affinity GABA plasma membrane transporter GAT-1 in the barrel cortex of mice 24 h after associative learning paradigm.

Interneurons containing somatostatin are affected by learning-induced cortical plasticity.

The maintenance of neural circuit stability is a dynamic process that requires the plasticity of many cellular and synaptic components. By changing the excitatory/inhibitory balance, inhibitory GABAergic plasticity can regulate excitability, and contribute to neural circuit function and refinement in learning and memory. Increased inhibitory GABAergic neurotransmission has been shown in brain structures involved in the learning process.

Fear learning increases the number of polyribosomes associated with excitatory and inhibitory synapses in the barrel cortex.

Associative fear learning, resulting from whisker stimulation paired with application of a mild electric shock to the tail in a classical conditioning paradigm, changes the motor behavior of mice and modifies the cortical functional representation of sensory receptors involved in the conditioning. It also induces the formation of new inhibitory synapses on double-synapse spines of the cognate barrel hollows. We studied density and distribution of polyribosomes, the putative structural markers of enhanced synaptic activation, following conditioning.

Rapid, learning-induced inhibitory synaptogenesis in murine barrel field.

The structure of neurons changes during development and in response to injury or alteration in sensory experience. Changes occur in the number, shape, and dimensions of dendritic spines together with their synapses. However, precise data on these changes in response to learning are sparse.

Impairment of experience-dependent cortical plasticity in aged mice.

This study addresses the relationship between aging and experience-dependent plasticity in the mouse somatosensory cortex. Plasticity in the cortical representation of vibrissae (whiskers) was investigated in young (3 months), mature (14 months) and old (2 years) mice using [14C]2-deoxyglucose (2-DG) autoradiography. Plastic changes were evoked using two experimental paradigms.

Characterization and plasticity of the double synapse spines in the barrel cortex of the mouse.

The somatosensory barrel cortex of rodents and its afferent pathway from the facial vibrissae is a very useful model for studying neuronal plasticity. Dendritic spines are the most labile elements of synaptic circuitry and the most likely substrate of experience-dependent alterations in neuronal circuits in cerebral cortex. We characterized morphologically and numerically a specific population of spines, i.

GAD67-positive puncta: contributors to learning-dependent plasticity in the barrel cortex of adult mice.

We have previously shown that a classical aversive conditioning paradigm involving stimulation of a row of facial vibrissae (whiskers) in the mouse produced expansion of the cortical representation of the activated vibrissae ("trained row"). This was demonstrated by labeling with 2-deoxyglucose (2DG) in layer IV of the barrel cortex. We have also shown that functional reorganization of the S1 cortex is accompanied by increases in the density of small GABAergic cells, and in GAD67 mRNA in the hollows of barrels representing the "trained row".

Short-term sensory learning does not alter parvalbumin neurons in the barrel cortex of adult mice: a double-labeling study.

We have previously reported that a classical conditioning paradigm involving stimulation of a row of facial vibrissae produced expansion of the cortical representation of the activated vibrissae ("trained row"), this was demonstrated by labeling with 2-deoxyglucose in layer IV of the barrel cortex. We have also shown that functional reorganization of the primary somatosensory cortex is accompanied by an increase in the density of small GABAergic cells and glutamate decarboxylase 67-positive neurons in the hollows of barrels representing the "trained row." GABA neurons of the rat neocortex co-localize with calcium-binding proteins [parvalbumin, carletinin, calbindin D28k] and neuropeptides (vasoactive intestinal polypeptide, somatostatin).

Learning-induced plasticity of cortical representations does not affect GAD65 mRNA expression and immunolabeling of cortical neuropil.

Two forms of glutamic acid decarboxylase (GAD) are present in inhibitory neurons of the mammalian brain, a 65-kDa isoform (GAD65) and a 67-kDa isoform (GAD67). We have previously found that GAD67 is upregulated during learning-dependent plasticity of cortical vibrissal representations of adult mice. After sensory conditioning involving pairing stimulation of vibrissae with a tail shock, the increase in mRNA expression and density of GAD67-immunoreactive neurons was observed in barrels representing vibrissae activated during the training.

Experience-dependent changes in cortical whisker representation in the adult mouse: a 2-deoxyglucose study.

Sensory experience and learning can modify cortical body maps. We have previously reported that 3 days of classical conditioning, in which stimulation of a row of whiskers was paired with tail shock, produced an expansion of the cortical representation of the "trained row" labeled with 2-deoxyglucose (2DG), in layer IIIb and IV of the barrel cortex. The present study examined plastic remodelling of the vibrissal cortical representation after pairing whisker stimulation with a drop of sweet water.

Rapid regulation of GAD67 mRNA and protein level in cortical neurons after sensory learning.

Cortical representations of different modalities can be modified by sensory learning. Our previous studies in the barrel cortex showed that expansion of the cortical representation of a row of vibrissae could be induced by pairing stimulation of a row of vibrissae with a tail shock. The plastic change in cortical reactivity to the input used during the training was accompanied by increased density of GABA immunoreactive neurons in the involved row of cortical barrels.

GABA immunoreactivity in mouse barrel field after aversive and appetitive classical conditioning training involving facial vibrissae.

We have previously reported that a classical conditioning paradigm involving stimulation of a row of facial vibrissae produced an expansion of the cortical representation of the "trained row", labeled with 2-deoxyglucose (2DG), in layer IV of the barrel field. The present study has examined the pattern of GABA immunoreactivity (GABA-IR) in the cortical representation of row B of the facial vibrissae after (i) 3 days of aversive training, and (ii) 2 months of appetitive training, where stimulation of row B of vibrissae on one side of the snout was used as a conditioned stimulus. The most notable observation was a greater density of GABA-IR cells concentrated in the hollows of the "trained row" B barrels compared to the hollows in the barrel field of the opposite hemisphere in the same mouse.

Learning-induced expansion of cortical maps--what happens to adjacent cortical representations?

The present study was designed to investigate the effects of learning-dependent enlargement of cortical representation of a row of vibrissae upon the appearance of adjacent cortical representations. We have found previously that three sessions of classical conditioning, during which stimulation of row B of vibrissae is paired with a tail shock, result in an increase of cortical representation of the trained row, as visualized with 2-deoxyglucose (2DG) metabolic functional mapping. In the present experiment, after the training in which row B was stimulated, we mapped with 2DG the cortical representations of rows A and C, not stimulated during the training.

Short-lasting classical conditioning induces reversible changes of representational maps of vibrissae in mouse SI cortex--a 2DG study.

It has been known for several years that receptive field properties of sensory cortical neurons can be altered by learning experiences. We attempted to visualize a global change of the cortical body map induced by learning. In order to do this a short-duration classical conditioning involving stimulation of a row of mystacial vibrissae in mice was followed with 2-deoxyglucose (2DG) mapping of functional activity.

Overlap of sensory representations in rat barrel cortex after neonatal vibrissectomy.

Cortical representation of the common fur of mystacial pad is situated outside postero-medial barrel subfield (PMBSF) in rat primary somatosensory cortex. Following neonatal vibrissectomy, stimulation of the common fur activates the neurones in PMBSF. We examined if sparing of one mystacial vibrissa from the neonatal ablation, which results in a very extensive increase of its cortical representation, would prevent the invasion of the common fur inputs into the PMBSF.

Partial blocking of NMDA receptors restricts plastic changes in adult mouse barrel cortex.

Changes of cortical body maps can be evoked in brains of adult animals by injury to sensory nerves. We investigated changes of functional representation of row C of mystacial vibrissae in the barrel cortex of mice. Plastic changes of cortical representations were mapped with 2-deoxyglucose autoradiography.

Temporal dynamics and regional distribution of [14C]serine uptake into mouse brain.

In order to examine the uptake of L-serine into brain structures and brain metabolic compartments, L-[U-14C]serine was injected into tail vein of mice. The uptake was examined 30 min, 90 min, 3 h and 5 h after injection by both quantitative autoradiography of coronal brain sections and by biochemical analysis. Brain radioactivity was extracted and partitioned into protein associated pellets, metabolites soluble in aqueous phase and lipids soluble in the organic phase.

Plasticity of mystacial fur representation in SI cortex of adult vibrissectomized rats--a 2DG study.

Localization of cortical representation of the common fur of mystacial pads was mapped with 2-deoxyglucose autoradiography in adult rats after vibrissectomy. Normal representation of mystacial fur was found in locations outside the posteromedial barrel subfield (PMBSF). Vibrissectomy performed in young adult resulted in fur inputs activating the PMBSF.

Short term changes of cortical body maps following partial vibrissectomy in adult mice.

Vibrissae-to-barrels pathway is often used as a model for investigating CNS plasticity. We examined early changes in the cortical representation of row C of vibrissae in adult mice, following vibrissectomy removing all whiskers except row C. The changes of cortical representation of the spared row of vibrissae were mapped with 2-deoxyglucose autoradiography.

Reduction of GABAA receptor binding of [3H]muscimol in the barrel field of mice after peripheral denervation: transient and long-lasting effects.

The effect of peripheral sensory deprivation upon GABAA receptor binding of [3H]muscimol was investigated in the barrel cortex--cortical representation of mystacial vibrissae of mice--by means of in vitro quantitative autoradiography. Unilateral lesions of all vibrissae or selected rows of whiskers were performed neonatally or in adulthood. [3H]muscimol binding was examined after various survival times up to 60 days.

Loss of glutamate immunoreactivity from mouse first somatosensory (SI) cortex following neonatal vibrissal lesion.

Whisker follicles were surgically ablated (lesioned) on two entire rows (B and C) of the left snout of two groups of Swiss mice, in the first 2 days after birth (neonatally lesioned) with the animals being allowed to survive for 4 weeks. In the second group at 8 weeks of age (adults), the whisker follicles of rows B and C were similarly lesioned and a survival period of 3 days allowed. Glutamate-immunoreactivity (Glu-IR) was examined in tangential sections of the first somatosensory (SI) 'barrel' cortex of these two groups (at which time it was also confirmed that the follicles had not regrown).