Tonic inhibition originates from synapses close to the soma

Soltész, Iván; Smetters, Diana K.; Módy, István

doi:10.1016/0896-6273(95)90274-0

Cited by 208 publications

(182 citation statements)

References 52 publications

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“…1B), which were completely blocked by PTX (40 M), a GABA A antagonist, but not by 2 mM kynurenic acid, a broad-spectrum excitatory amino acid antagonist. These spontaneous synaptic GABA A currents may arise from spontaneous PC discharge, or from APindependent GABA release (46). It is conceivable that the in vivo frequency of the spontaneous GABA A currents may be much higher than those presented here because many innervating PCs were severed from the slices.…”

Section: Basal and Evoked Gabaergic Inputs To The Cerebellar Nuclear mentioning

confidence: 60%

Cerebellar cortical inhibition and classical eyeblink conditioning

Bao

Chen

Kim

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

124

110

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The cerebellum is considered a brain structure in which memories for learned motor responses (e.g., conditioned eyeblink responses) are stored. Within the cerebellum, however, the relative importance of the cortex and the deep nuclei in motor learning͞memory is not entirely clear. In this study, we show that the cerebellar cortex exerts both basal and stimulus-activated inhibition to the deep nuclei. Sequential application of a ␥-aminobutyric acid type A receptor (GABAAR) agonist and a noncompetitive GABAAR antagonist allows selective blockade of stimulus-activated inhibition. By using the same sequential agonist and antagonist methods in behaving animals, we demonstrate that the conditioned response (CR) expression and timing are completely dissociable and involve different inhibitory inputs; although the basal inhibition modulates CR expression, the conditioned stimulus-activated inhibition is required for the proper timing of the CR. In addition, complete blockade of cerebellar deep nuclear GABAARs prevents CR acquisition. Together, these results suggest that different aspects of the memories for eyeblink CRs are encoded in the cerebellar cortex and the cerebellar deep nuclei.learning ͉ memory ͉ cerebellar deep nuclei ͉ cerebellar cortex ͉ ␥-aminobutyric acid B ecause of the highly organized cytoarchitecture of its numerous neurons, the cerebellum has long been considered as a neuronal substrate for some forms of learning and memory (1-4). Accumulating evidence supports this view by demonstrating the critical roles of the cerebellum in motor learning (5-10). On the basis of empirical results and theoretical models, the basic neural circuitries underlying motor learning, such as classical conditioning and vestibulo-ocular-reflex adaptation, have been delineated (6,8,9). For example, in classical eyeblink conditioning, mossy fibers (mf) and climbing fibers (cf) are thought to convey conditioned stimulus (CS) and unconditioned stimulus (US) signals, respectively, to both the cerebellar cortex and the deep nuclei. Various types of synaptic plasticity have been demonstrated in these regions, including parallel fiberPurkinje cell long-term depression (pf-PC LTD) (11, 12) and long-term potentiation (pf-PC LTP) (13), pf-PC ␥-aminobutyric acid (GABA)-transmitting rebound potentiation (14), PC-deep nuclear neuron (DNN) LTD (15, 16), and LTP of extracellular responses in the cerebellar deep nuclei (17). These different types of plasticity may be involved in supporting learning in both the cerebellar cortex and deep nuclei (10,18,19).Although the early theoretical models only concerned the cerebellar cortex, recent studies implicated both the cortex and the deep nuclei in motor learning. Discrete lesions of the cerebellar interpositus nucleus (electrolytically, chemically, reversibly) consistently and completely prevent the acquisition and permanently and completely abolished retention͞expression of classically conditioned eyeblink responses in rabbits, rats, and mice (20-28). Cortical lesions affect various aspects of l...

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Section: Basal and Evoked Gabaergic Inputs To The Cerebellar Nuclear mentioning

confidence: 60%

Cerebellar cortical inhibition and classical eyeblink conditioning

Bao

Chen

Kim

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

124

110

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“…Lateral fluid percussion injury (LFPI) reproducibly damages this structure, and causes cognitive impairment (3,4) and regional shifts in network excitability in both area CA1 (decreased net synaptic efficacy) and dentate gyrus (increased net synaptic efficacy) (4)(5)(6)(7).…”

mentioning

confidence: 99%

Dietary branched chain amino acids ameliorate injury-induced cognitive impairment

Cole¹,

Mitala²,

Kundu³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

130

139

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Neurological dysfunction caused by traumatic brain injury results in profound changes in net synaptic efficacy, leading to impaired cognition. Because excitability is directly controlled by the balance of excitatory and inhibitory activity, underlying mechanisms causing these changes were investigated using lateral fluid percussion brain injury in mice. Although injury-induced shifts in net synaptic efficacy were not accompanied by changes in hippocampal glutamate and GABA levels, significant reductions were seen in the concentration of branched chain amino acids (BCAAs), which are key precursors to de novo glutamate synthesis. Dietary consumption of BCAAs restored hippocampal BCAA concentrations to normal, reversed injury-induced shifts in net synaptic efficacy, and led to reinstatement of cognitive performance after concussive brain injury. All brain-injured mice that consumed BCAAs demonstrated cognitive improvement with a simultaneous restoration in net synaptic efficacy. Posttraumatic changes in the expression of cytosolic branched chain aminotransferase, branched chain ketoacid dehydrogenase, glutamate dehydrogenase, and glutamic acid decarboxylase support a perturbation of BCAA and neurotransmitter metabolism. Ex vivo application of BCAAs to hippocampal slices from injured animals restored posttraumatic regional shifts in net synaptic efficacy as measured by field excitatory postsynaptic potentials. These results suggest that dietary BCAA intervention could promote cognitive improvement by restoring hippocampal function after a traumatic brain injury.

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“…The pyramdial neuron receives functionally segregated inputs in its apical dendrites and basal dendrites from diverse cortical and subcortical regions (see Table 1). The GABAergic interneuron exerts tonic hyperpolarizing action in the apical dendrites, as well as in the somatic region of the pyramidal cell (Soltesz et al 1995;Miles et al 1996;Kim et al 1995). The modulatory inputs to the pyramidal dendrite by the GABAergic interneurons can, in turn, be regulated by mesocortical dopamine inputs to these interneurons.…”

Section: Synthesis Of a Neuronal Model Of Schizophrenia Based On The mentioning

confidence: 99%

Developing a Neuronal Model for the Pathophysiology of Schizophrenia Based on the Nature of Electrophysiological Actions of Dopamine in the Prefrontal Cortex

Yang

Seamans

Gorelova

1999

Neuropsychopharmacology

164

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This review covers some recent findings of the electrophysiological mechanisms through which mesocortical dopamine modulates prefrontal cortical neurons. Dopamine has been shown to modulate several ionic conductances located along the soma-dendritic axis of prefrontal cortical pyramidal neurons. These ionic currents include high-voltage-activated calcium currents and slowly inactivating NaReceived May 12, 1998; revised May 27, 1998; accepted May 29, 1998. 162 C.R. Yang et al. N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 21 , NO Schizophrenia strikes one in one hundred people worldwide, regardless of cultural or racial origins. As the illness progresses and if it remains unattended, patients are frequently trapped in psychological, social, and economic devastation (Gottesman 1991;Jablensky 1995). Currently, our incomplete understanding of the neurobiological bases of schizophrenia suggests that defects in the genetic controls of brain development in such limbic regions (including temporal lobe structures such as hippocampus and the amygdala) as well as the prefrontal cortex (PFC) lead to cell loss or deformation, cytoarchitectural disorganization, and abnormal innervation in these brain regions (Roberts and Bruton 1990;Stevens 1992; Bogerts 1993;Shapiro 1993; Akbarian et al. 1993 Akbarian et al. , 1996Ross and Pearlson 1996;Weinberger 1996; Karayiorgou and Gogos 1997; Lewis 1997;Selemon et al. 1995Selemon et al. , 1998.Some results from recent imaging studies of brains from living schizophrenics have suggested that there are defective functional communications between the interconnected cortical (PFC and cingulate cortex) and limbic subcortical structures (thalamus, striatum, and temporal lobe limbic structures)(see reviews of Liddle 1996; Pfefferbaum and Marsh 1995; Andreasen 1997; Heckers et al. 1998). Findings from these studies suggest that in schizophrenics, abnormal recruitment of several interconnected cortical and subcortical structures may underlie such symptom clusters as psychomotor poverty, thought disorganization, and reality distortion (Liddle et al. 1992; Liddle 1996; Fletcher 1998; Heckers et al. 1998).As noted in Figure 1, the PFC receives converging limbic, association cortical, and mesocortical dopamine inputs. These inputs interact in the PFC and are involved functionally in high-level cognitive processes (Fuster 1995). Among the many brain regions that PFC output innervates, two important subcortical regions are emphasized in this review. These are the nucleus accumbens (where mesoaccumbens dopamine neurons terminate) and the ventral tegmental area (VTA, where the midbrain dopamine neurons reside) Groenewegen et al. 1990; Berendse et al. 1992a Berendse et al. , 1992bSesack and Pickel 1992;Gorelova and Yang 1997b). Several of the interconnected limbic, cortical, and subcortical structures known to be affected in schizophrenia are targets of the ascending midbrain dopamine systems that normally provide functional modulation of neurotransmission (Björklund and Lindvall 1984;Mogenson et ...

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Tonic inhibition originates from synapses close to the soma

Cited by 208 publications

References 52 publications

Cerebellar cortical inhibition and classical eyeblink conditioning

Cerebellar cortical inhibition and classical eyeblink conditioning

Dietary branched chain amino acids ameliorate injury-induced cognitive impairment

Developing a Neuronal Model for the Pathophysiology of Schizophrenia Based on the Nature of Electrophysiological Actions of Dopamine in the Prefrontal Cortex

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