Biomedical subjects

Alberto Bacci

Publications and source records attributed to Alberto Bacci.

9 recordsLinked to original sources

PubMed2006

Enhancement of spike-timing precision by autaptic transmission in neocortical inhibitory interneurons.

In vivo studies suggest that precise firing of neurons is important for correct sensory representation. Principal neocortical neurons fire imprecisely when repeatedly activated by fixed sensory stimuli or current depolarizations. Here we show that in contrast to pyramidal neurons, firing in neocortical GABAergic fast-spiking (FS) interneurons is quite precise. FS interneurons are self-innervated by powerful GABAergic autaptic connections reliably activated after each spike, suggesting that autapses strongly regulate FS-cell spike timing. Indeed, blockade of autaptic transmission degraded temporal precision in multiple ways. Under these conditions, realistic dynamic-clamp hyperpolarizing autapses restored precision of spike timing, even in the presence of synaptic noise. Furthermore, firing precision was increased in pyramidal neurons by artificial GABAergic autaptic conductances, suggesting that tightly coupled synaptic feedback inhibition regulates spike timing in principal cells. Thus, well-timed inhibition, whether autaptic or synaptic, facilitates precise spike timing and promotes synchronized cortical network oscillations relevant to several behaviors.

Action Potentials↗

PubMed2005

Modulation of neocortical interneurons: extrinsic influences and exercises in self-control.

Neocortical GABAergic interneurons are a highly heterogeneous cell population that forms complex functional networks and has key roles in information processing within the cerebral cortex. Mechanisms that control the output of these cells are therefore crucial in regulating excitability within the neocortex during normal and pathophysiological activities. In addition to subtype-specific modulation of GABAergic cells by neurotransmitters released by afferents from subcortical nuclei, interneurons belonging to different classes are controlled by distinct self-modulatory mechanisms, each unique and powerful. In this article, we review the diverse responses of neocortical interneurons to extrinsic and intrinsic neuromodulators. We discuss how specificity of responses might differentially influence inhibition in somatodendritic compartments of pyramidal neurons and affect the balance of activities in neocortical circuits.

Animals↗

PubMed2004

Long-lasting self-inhibition of neocortical interneurons mediated by endocannabinoids.

Neocortical GABA-containing interneurons form complex functional networks responsible for feedforward and feedback inhibition and for the generation of cortical oscillations associated with several behavioural functions. We previously reported that fast-spiking (FS), but not low-threshold-spiking (LTS), neocortical interneurons from rats generate a fast and precise self-inhibition mediated by inhibitory autaptic transmission. Here we show that LTS cells possess a different form of self-inhibition. LTS, but not FS, interneurons undergo a prominent hyperpolarization mediated by an increased K+-channel conductance. This self-induced inhibition lasts for many minutes, is dependent on an increase in intracellular [Ca2+] and is blocked by the cannabinoid receptor antagonist AM251, indicating that it is mediated by the autocrine release of endogenous cannabinoids. Endocannabinoid-mediated slow self-inhibition represents a powerful and long-lasting mechanism that alters the intrinsic excitability of LTS neurons, which selectively target the major site of excitatory connections onto pyramidal neurons; that is, their dendrites. Thus, modulation of LTS networks after their sustained firing will lead to long-lasting changes of glutamate-mediated synaptic strength in pyramidal neurons, with consequences during normal and pathophysiological cortical network activities.

Animals↗

PubMed2003

Major differences in inhibitory synaptic transmission onto two neocortical interneuron subclasses.

Locally projecting GABAergic interneurons are the major providers of inhibition in the neocortex and play a crucial role in several brain functions. Neocortical interneurons are connected via electrical and chemical synapses that may be crucial in modulating complex network oscillations. We investigated the properties of spontaneous and evoked IPSCs in two morphologically and physiologically identified interneuron subtypes, the fast-spiking (FS) and low threshold-spiking (LTS) cells in layer V of rodent sensorimotor cortex. We found that IPSCs recorded in FS cells were several orders of magnitude more frequent, larger in amplitude, and had faster kinetics than IPSCs recorded in LTS cells. GABA(A) receptor alpha- and beta-subunit selective modulators, zolpidem and loreclezole, had different effects on IPSCs in FS and LTS interneurons, suggesting differential expression of GABA(A) receptor subunit subtypes. These pharmacological data indicated that the alpha1 subunit subtype is poorly expressed by LTS cells but makes a large contribution to GABA(A) receptors on FS cells. This was confirmed by experiments performed in genetically modified mice in which the alpha1 subunit had been made insensitive to benzodiazepine-like agonists. These results suggest that differences in IPSC waveform are likely attributable to distinctive expression of GABA(A) receptor subunits in FS and LTS cells. The particular properties of GABAergic input on different interneuronal subtypes might have important consequences for generation and pacing of cortical rhythms underlying several brain functions. Moreover, selective pharmacological manipulation of distinct inhibitory circuits might allow regulation of pyramidal cell activities under specific physiological and pathophysiological conditions.

Action Potentials↗

PubMed2003

Functional autaptic neurotransmission in fast-spiking interneurons: a novel form of feedback inhibition in the neocortex.

Autapses are synapses made by a neuron onto itself. Although morphological evidence for existence of autapses has been reported in several brain areas, it is not known whether such self-innervation in the neocortex is functional and robust. Here we report that GABAergic autaptic activity is present in fast-spiking, but not in low-threshold spiking, interneurons of layer V in neocortical slices. Recordings made with the perforated-patch technique, in which physiological intracellular chloride homeostasis was unperturbed, demonstrated that autaptic activity has significant inhibitory effects on repetitive firing and increased the current threshold for evoking action potentials. These results show that autapses are not rudimentary nonfunctional structures, but rather they provide a novel and powerful form of feedback inhibitory synaptic transmission in one class of cortical interneurons.

Action Potentials↗

PubMed2002

Differential modulation of synaptic transmission by neuropeptide Y in rat neocortical neurons.

Neuropeptide Y (NPY) is widely expressed throughout the nervous system and is known to reduce excitatory (but also inhibitory) synaptic transmission in many CNS areas, leading to the proposal that it is an endogenous antiepileptic agent. In the neocortex, where NPY is present in gamma-aminobutyric acid (GABA)ergic interneurons, its effects on inhibitory and excitatory synaptic activities have not been completely explored. Here we report that NPY application elicits a long-lasting decrease in evoked excitatory postsynaptic current amplitude and a delayed, long-lasting increase in the amplitude of evoked monosynaptic inhibitory postsynaptic current (IPSC) in layer V pyramidal neurons of rat neocortex. The novel, late, NPY-mediated increase of inhibitory synaptic transmission is caused by modulation of Ca2+-dependent GABA release onto pyramidal neurons, as it was accompanied by an increase in Ca2+-dependent miniature IPSC frequency. NPY decreased evoked monosynaptic IPSCs in GABAergic interneurons, indicating that this neuropeptide has differential effects on different neuronal subtypes in the neocortex. Each of these NPY actions would decrease excitability in cortical circuits, a result that has important implications for both physiological neocortical operations as well as pathophysiological epileptiform activities.

Animals↗

PubMed2002

A developmental switch of AMPA receptor subunits in neocortical pyramidal neurons.

AMPA receptors mediate most of the fast excitatory neurotransmission in the brain, and those lacking the glutamate receptor 2 (GluR2) subunit are Ca(2+)-permeable and expressed in cortical structures primarily by inhibitory interneurons. Here we report that synaptic AMPA receptors of excitatory layer 5 pyramidal neurons in the rat neocortex are deficient in GluR2 in early development, approximately before postnatal day 16, as evidenced by their inwardly rectifying current-voltage relationship, blockade of AMPA receptor-mediated EPSCs by external and internal polyamines, permeability to Ca(2+), and GluR2 immunoreactivity. Overall, these results indicate that neocortical pyramidal neurons undergo a developmental switch in the Ca(2+) permeability of their AMPA receptors through an alteration of their subunit composition. This has important implications for plasticity and neurotoxicity.

Aging↗

PubMed2002

Localization and functional relevance of system a neutral amino acid transporters in cultured hippocampal neurons.

Glutamine and alanine are important precursors for the synthesis of glutamate. Provided to neurons by neighboring astrocytes, these amino acids are internalized by classical system A amino acid carriers. In particular, System A transporter (SAT1) is a highly efficient glutamine transporter, whereas SAT2 exhibits broad specificity for neutral amino acids with a preference for alanine. We investigated the localization and the functional relevance of SAT1 and SAT2 in primary cultures of hippocampal neurons. Both carriers have been expressed since early developmental stages and are uniformly distributed throughout all neuronal processes. However, whereas SAT1 is present in axonal growth cones and can be detected at later developmental stages at the sites of synaptic contacts, SAT2 does not appear to be significantly expressed in these compartments. The non-metabolizable amino acid analogue alpha-(methylamino)-isobutyric acid, a competitive inhibitor of system A carriers, significantly reduced miniature excitatory postsynaptic current amplitude in neurons growing on top of astrocytes, being ineffective in pure neuronal cultures. alpha-(Methylamino)-isobutyric acid did not alter neuronal responsitivity to glutamate, thus excluding a postsynaptic effect. These data indicate that system A carriers are expressed with a different subcellular distribution in hippocampal neurons and play a crucial role in controlling the astrocyte-mediated supply of glutamatergic neurons with neurotransmitter precursors.

Amino Acid Transport System A↗

PubMed2002

Block of glutamate-glutamine cycle between astrocytes and neurons inhibits epileptiform activity in hippocampus.

Recurrent epileptiform activity occurs spontaneously in cultured CNS neurons and in brain slices in which GABA inhibition has been blocked. We demonstrate here that pharmacological treatments resulting in either the block of glutamine production by astrocytes or the inhibition of glutamine uptake by neurons suppress or markedly decrease the frequency of spontaneous epileptiform discharges both in primary hippocampal cultures and in disinhibited hippocampal slices. These data point to an important role for the neuron-astrocyte metabolic interaction in sustaining episodes of intense rhythmic activity in the CNS, and thereby reveal a new potential target for antiepileptic treatments.

Animals↗