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Biomedical subjects

G G Turrigiano

Publications and source records attributed to G G Turrigiano.

25 records · Page 2Linked to original sources

Partial purification, tissue distribution and modulatory activity of a crustacean cholecystokinin-like peptide.

Reversed-phase chromatography was used to separate several forms of cholecystokinin-like peptides (CCKLP) from the pericardial organs (PCOs) of the spiny lobster Panulirus interruptus. Fast protein liquid chromatography of PCOs, stomatogastric ganglia (STGs) and eyestalks revealed five peaks of CCKLP (peaks A-E) that were common to all three tissues, as well as two additional peaks (peaks F and G) in the STG. Peaks A-E were present in the hemolymph of fed, but not starved, lobsters. The bioactivity of peaks A-E was tested on the gastric mill rhythm of the isolated STG. Only peak E elicited activity. The effects of peak E included activating the gastric mill rhythm in quiescent preparations and strengthening existing rhythms in a dose-dependent manner. Further purification of peak E by high performance liquid chromatography resolved this peak into two immunoreactive peaks, one of which retained its bioactivity. The effects of peak E were blocked by the CCK antagonist proglumide. These results are consistent with a role for peak E in the feeding-induced activation of the gastric mill.

Animals↗

Modulation of identified stomatogastric ganglion neurons in primary cell culture.

1. We studied the properties of identified stomatogastric ganglion (STG) neurons grown in complete isolation in primary cell culture. 2. STG neurons isolated with a short piece of primary neurite adhered to the culture dishes and extended neurites. Outgrowth was apparent within several hours, and continued for < or = 5 days. 3. After 1 day in culture, most STG neurons were not capable of producing action potentials or oscillations. After 3-5 days in culture, most STG neurons regained the ability to fire action potentials, and some became endogenous bursters. Neurons in culture 3-5 days possessed many of the physiological properties of STG neurons in situ, including postinhibitory rebound, a hyperpolarization-activated depolarizing voltage sag, and the ability to burst in the presence of the potassium channel blocker tetraethyl-ammonium. 4. Identified cultured neurons responded appropriately to a variety of neuromodulators, including the monoamines dopamine and octopamine, the muscarinic agonist pilocarpine, and the peptide proctolin. These data suggest that the maintenance of receptor expression in fully differentiated STG neurons is not affected by isolation from all synaptic and modulatory influences. 5. In contrast to the other modulators tested, the effects of serotonin on cultured neurons differed from those reported in situ. Two cell types that are reported to be hyperpolarized by serotonin in situ, the lateral pyloric and pyloric neurons, were depolarized by serotonin in culture.

Action Potentials↗

Frequency and burst duration in oscillating neurons and two-cell networks.

We study the relationship of injected current to oscillator period in single neurons and two-cell model networks formed by reciprocal inhibitory synapses. Using a Morris-Lecar-like model, we identify two qualitative types of oscillatory behavior for single model neurons. The "classical" oscillator behavior is defined as type A. Here the burst duration is relatively constant and the frequency increases with depolarization. For oscillator type B, the frequency first increases and then decreases when depolarized, due to the variable burst duration. Our simulations show that relatively modest changes in the maximal inward and outward conductances can move the oscillator from one type to another. Cultured stomatogastric ganglion neurons exhibit both A and B type behaviors and can switch between the two types with pharmacological manipulation. Our simulations indicate that the stability of a two-cell network with injected current can be extended with inhibitory coupling. In addition, two-cell networks formed from type A or type B oscillators behave differently from each other at lower synaptic strengths.

Animals↗

Distribution of cholecystokinin-like immunoreactivity within the stomatogastric nervous systems of four species of decapod crustacea.

The distribution of cholecystokinin-like immunoreactivity was studied in the stomatogastric nervous systems, pericardial organs, and haemolymph of four species of decapod crustacea, by using immunocytochemical and radioimmunoassay techniques. Whereas cholecystokinin-like immunoreactivity was found within the stomatogastric nervous systems of all four species, its distribution in each is unique. Two species (Panulirus interruptus and Homarus americanus) have cholecystokinin-like immunoreactivity within fibers and neuropil of the stomatogastric ganglion (STG); two other species (Cancer antenarius and Procambarus clarkii) do not. Further, the cholecystokinin-like immunoreactivity within the STGs of Panulirus and Homarus arise from distinct structures; from a projection of anterior ganglia in Panulirus, and from somata within the posterior motor nerves in Homarus. The staining in the other ganglia of the stomatogastric nervous system also shows some interspecies variability, although it appears to be more highly conserved than staining within the STG. These differences in staining were confirmed by measuring the amount of CCK-like peptide present in tissue extracts of ganglia by radioimmunoassay. In contrast to the variable staining within the STG, all four species have cholecystokinin-like immunoreactivity within the neurosecretory pericardial organs and thoracic segmental nerves. This cholecystokinin-like immunoreactivity is contained within fibers and within varicosities that coat the surface of these structures. The location of this staining and the presence of detectible levels of CCK-like peptide in the haemolymph suggests that CCK-like peptides in decapod crustacea may be utilized as neurohormones.

Animals↗

A cholecystokinin-like hormone activates a feeding-related neural circuit in lobster.

The peptide hormone cholecystokinin (CCK) contributes to the production of feeding-related behaviour in mammals, but the mechanism by which it exerts its effects remains unclear. The gastric mill neural circuit of lobster is an experimentally accessible model system for studying the hormonal control of feeding-related behaviour. Composed of 11 identified neurons, this circuit produces rhythmic movement of teeth within the stomach. We have previously shown that the gastric mill motor pattern can be modulated by a cholecystokinin-like peptide in vitro. We report here that (1) after feeding, levels of CCK-like peptide in haemolymph increase with the activation of the gastric mill, (2) injections of CCK activate the gastric mill, and (3) a specific CCK antagonist inhibits feeding-induced gastric mill activity. This neatly demonstrates a casual link between in vivo release of a peptide hormone and activation of a neural circuit.

Animals↗

Cholecystokinin-like peptide is a modulator of a crustacean central pattern generator.

The presence, release, and physiological effects of a cholecystokinin(CCK)-like peptide within the stomatogastric ganglion (STG) of the lobster, Panulirus interruptus, are described. Indirect immunofluorescence with 2 antisera raised against CCK8 was used to determine the distribution of CCK-like immunoreactivity (CCKLI) in the stomatogastric nervous system. CCKLI was demonstrated in the input nerve and the neuropil of the STG and in neuropil and somata in the commissural ganglia (CGs), brain, and eyestalks. None of the somata within the STG displayed CCKLI. The cross-reactivities of the CCK antisera with several peptides were determined using either a radioimmunoassay or an immunoblot assay; the antisera recognized peptides homologous to CCK but did not cross-react significantly with several unrelated peptides. The STG contains 2 central pattern generators (CPGs), the pyloric and the gastric mill CPGs. Bath application of CCK8 to the STG had modulatory effects on both CPGs, which were dose dependent and reversible. CCK increased the spike frequencies and number of spikes per burst of the pyloric rhythm but had little effect on the period. CCK increased the period of the gastric rhythm and produced changes in the spike frequencies, burst lengths, and phases of gastric units. High concentrations of peptide were needed to produce these effects (10(-6) to 10(-4) M). Finally, stimulation of the stomatogastric nerve (stn), which contains fibers immunoreactive to CCK, produced calcium-dependent release of CCK molar equivalents (CCKE) into the STG. The stn was electrically stimulated and the superfusate around the ganglion was collected and assayed for CCKE using a radioimmunoassay. Stimulation produced the release of 37.1 +/- 7.1 fmol (mean +/- SEM), compared to 13.7 +/- 4.9 fmol for unstimulated controls and 4.9 +/- 2.9 fmol in the absence of calcium. These data suggest that a CCK-like peptide is an endogenous modulator of the stomatogastric ganglion of P. interruptus.

Animals↗

BDNF regulates the intrinsic excitability of cortical neurons.

Neocortical pyramidal neurons respond to prolonged activity blockade by modulating their balance of inward and outward currents to become more sensitive to synaptic input, possibly as a means of homeostatically regulating firing rates during periods of intense change in synapse number or strength. Here we show that this activity-dependent regulation of intrinsic excitability depends on the neurotrophin brain-derived neurotrophic factor (BDNF). In experiments on rat visual cortical cultures, we found that exogenous BDNF prevented, and a TrkB-IgG fusion protein reproduced, the change in pyramidal neuron excitability produced by activity blockade. Most of these effects were also observed in bipolar interneurons, indicating a very general role for BDNF in regulating neuronal excitability. Moreover, earlier work has demonstrated that BDNF mediates a different kind of homeostatic plasticity present in these same cultures: scaling of the quantal amplitude of AMPA-mediated synaptic inputs up or down as a function of activity. Taken together, these results suggest that BDNF may be the signal controlling a coordinated regulation of synaptic and intrinsic properties aimed at allowing cortical networks to adapt to long-lasting changes in activity.

Animals↗