Biomedical subjects

K Kandler

Publications and source records attributed to K Kandler.

12 recordsLinked to original sources

PubMed2000

New phototriggers: extending the p-hydroxyphenacyl pi-pi absorption range.

[equation--see text] Introducing 3-methoxy or 3,5-dimethoxy substituents on the 4-hydroxyphenacyl (pHP) photoremovable protecting group has been explored with two excitatory gamma-amino acids, L-glutamic acid and gamma-amino butyric acid (GABA). These substituents significantly extend the absorption range of the pHP chromophore, e.g., the tail of absorption bands of 2a,b extend above 400 nm, well beyond the absorptions of aromatic amino acids and nucleotides. Irradiation releases the amino acids with rate constants of approximately 10(7) s(-)(1) and appearance efficiencies (Phi(app)) of 0.03-0.04. The photoproducts are formed through the pHP excited triplet and are primarily products of photoreduction and photohydrolysis. 1a,b also rearranged to the phenylacetic acid 3.

Acetophenones↗

PubMed2000

Enhancement of NMDA receptor-mediated currents by light in rat neurones in vitro.

1. N-Methyl-D-aspartate (NMDA) receptor function can be modified by the action of several endogenous and exogenous modulatory processes. In the present study, we report that brief pulses of light potentiate NMDA, but not non-NMDA glutamatergic receptor-mediated whole-cell and single channel currents in rat cortical neurones in vitro. In addition, light also potentiated NMDA receptor-mediated whole-cell responses in isolated rat retinal neurones. 2. Potentiation of NMDA whole-cell currents in cortical neurones was readily observed during and following a brief (< 2 s) exposure of neurones to wavelengths of less than 324 nm of relatively bright light (0.09 microW microm-2). In addition, prolonged exposures (> 30 s) to visible wavelengths (> 380 nm) or to attenuated light (1-3 % transmittance of non-attenuated light) were also sufficient to enhance NMDA receptor-mediated responses. 3. The light-induced potentiation of NMDA receptor-mediated currents persisted for several minutes, slowly reversing to control levels with a time constant of approximately 5 min. A subsequent exposure to light could potentiate NMDA receptor-mediated currents for a second time. 4. Light did not alter the apparent affinity of the NMDA receptor for the co-agonists NMDA and glycine. Additionally, potentiation of the NMDA-induced currents was not mediated by a change in the pH sensitivity of the receptor. In excised outside-out membrane patches, the effects of light on NMDA-activated unitary currents were manifested as a twofold increase in channel open frequency without alterations in single channel amplitude or open time. 5. Our results suggest the presence of a light-sensitive moiety within the NMDA receptor, or in a closely associated structure, which affects channel properties. This previously unrecognized form of NMDA receptor modulation may provide a tool for understanding the conformational changes associated with its gating. In addition, it is possible that light may affect NMDA receptor-mediated function or dysfunction in the retina.

Animals↗

PubMed1998

Coordination of neuronal activity in developing visual cortex by gap junction-mediated biochemical communication.

During brain development, endogenously generated coordinated neuronal activity regulates the precision of developing synaptic circuits (Shatz and Stryker, 1988; Weliky and Katz, 1997). In the neonatal neocortex, a form of endogenous coordinated activity is present as locally restricted intercellular calcium waves that are mediated by gap junctions (Yuste et al., 1992). As in other neuronal and non-neuronal systems, these coordinated calcium fluctuations may form the basis of functional cell assemblies (for review, seeWarner, 1992; Peinado et al., 1993b). In the present study, we investigated the cellular mechanisms that mediate the activation of neuronal domains and the propagation of intercellular calcium waves in slices from neonatal rat neocortex. The occurrence of neuronal domains did not depend on intercellular propagation of regenerative electrical signals because domains persisted after blockade of sodium and calcium-dependent action potentials. Neuronal domains were elicited by intracellular infusion of inositol trisphosphate (IP3) but not of calcium, indicating the involvement of IP3-related second-messenger systems. Pharmacological stimulation of metabotropic glutamate receptors, which are linked to the production of IP3, elicited similarly coordinated calcium increases, whereas pharmacological blockade of metabotropic glutamate receptors dramatically reduced the number of neuronal domains. Therefore, the propagating cellular signal that causes the occurrence of neuronal domains seems to be inositol trisphosphate but not calcium. Because coordination of neuronal calcium changes by gap junctions is independent of electrical signals, the function of gap junctions between neocortical neurons is probably to synchronize biochemical rather than electrical activity.

Aging↗

PubMed1998

Focal photolysis of caged glutamate produces long-term depression of hippocampal glutamate receptors.

Separating contributions of pre- and postsynaptic factors to the maintenance of long-term potentiation (LTP) and long-term depression (LTD) has been confounded by their experimental interdependence. To isolate the postsynaptic contribution, glutamate-receptor-mediated currents were elicited by localized photolysis of caged glutamate in small spots along the dendrites of CA1 hippocampal pyramidal cells. With synaptic transmission blocked, pairing depolarization of pyramidal cells with repeated photolysis of caged glutamate at one site markedly and persistently depressed subsequent responses to glutamate; responses at a second, unpaired site were unchanged. Like synaptically induced LTD at the CA3-CA1 synapse, this depression was site specific, NMDA-receptor dependent and blocked by protein-phosphatase inhibitors. Thus, robust, persistent alterations of postsynaptic glutamate receptor efficacy can occur without presynaptic neurotransmitter release.

Animals↗

PubMed1998

Relationship between dye coupling and spontaneous activity in developing ferret visual cortex.

Neuronal coupling by gap junctions is common during early development of the brain. Coupling is thought to create functional cell assemblies which may be involved in the functional specification of brain areas and the formation of synaptic circuits. In the present study we used slices from the visual cortex of postnatal ferrets to investigate the temporal relationship of gap junction coupling and formation of functional synapses. Individual neurons were filled with the gap-junction-permeable dye biotin ethylenediamine while spontaneous synaptic currents were recorded using whole-cell patch clamp recording techniques. We found that dye coupling increased during the first 2 postnatal weeks resulting at a peak around P14, after which coupling steadily decreased until adult levels were reached in animals older than P30. Spontaneous synaptic activity increased 30-fold between birth and maturity (from 10.8 +/- 2.4 to 318 +/- 54 events/min). The sharpest rise in synaptic activity, an over 5-fold increase, occurred between P15 and P19, shortly after the invasion of thalamocortical fibers.

Animals↗

PubMed1995

Development of electrical membrane properties and discharge characteristics of superior olivary complex neurons in fetal and postnatal rats.

Although hearing onset occurs relatively late during ontogeny of rats [around postnatal day (P) 12], anatomical brainstem connections are formed much earlier and are present before birth, indicating that a substantial amount of maturation occurs without acoustic input. Electrical activity is thought to influence neuronal development, but the physiological properties of auditory brainstem neurons during perinatal maturation are barely known. The present study focuses on the development of electrophysiological membrane properties of neurons in the rat's superior olivary complex (SOC), the first binaural station in the mammalian auditory brainstem. In in vitro slice preparations, intracellular recordings were obtained from 115 SOC cells from embryonic day (E) 18 to P17, and cells were morphologically identified by intracellular injection of biocytin or neurobiotin. By E18, i.e. 4 days before birth, SOC neurons were capable of generating Na(+)-dependent action potentials. Several passive and active membrane properties, including the resting potential, spike threshold and spike amplitude, did not change with development. In contrast, input resistance, time constant and spike duration decreased significantly, and maximal spike frequency increased significantly during the age period sampled. Our results show that rat SOC neurons display mature as well as immature electrical membrane properties during the same developmental period when anatomical connections are refined and when the soma-dendritic morphology develops. We conclude, therefore, that their membrane properties represent adequate physiological adaptations to the immature auditory brainstem microcircuits and that they form a basis upon which the development of these microcircuits is shaped.

Acoustic Stimulation↗

PubMed1995

Patterns of excitation and inhibition evoked by horizontal connections in visual cortex share a common relationship to orientation columns.

Combined optical imaging and electrophysiological techniques were used to assess directly the functional nature of long-range excitatory and inhibitory synaptic interactions between orientation columns in area 17 of ferret visual cortex. A significant correlation was found between the layout of iso-orientation columns and the pattern of evoked synaptic inputs between cortical sites: the largest-amplitude inhibitory and excitatory synaptic responses were evoked in single neurons when stimulation and recording electrodes were located in orientation columns sharing the same angle preference. Both excitatory and inhibitory synaptic responses decreased in amplitude when stimulation and recording electrodes were located in orientation columns with orthogonal angle preferences. Changing the stimulus intensity altered the balance of evoked excitation and inhibition without changing the columnar specificity of inputs. These results directly demonstrate that horizontal connections modulate both excitatory and inhibitory synaptic interactions between iso-orientation columns.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1995

Neuronal coupling and uncoupling in the developing nervous system.

Sensitive new tracers and imaging techniques have revealed that gap junction coupling during brain development is much more pronounced than previously believed. Recent results demonstrate that cell coupling can produce functional neuron assemblies characterized by synchronized fluctuations in the cytosolic Ca2+ concentration. Coupling is especially pronounced before and during the period of synapse formation and initial establishment of neuronal circuits. Thus, communication via gap junctions may generate coordinated electrical or biochemical activity before the onset of synaptic transmission, and thereby provide the outlines of functional architecture in the developing brain.

Animals↗

PubMed1995

Development of glycinergic and glutamatergic synaptic transmission in the auditory brainstem of perinatal rats.

In contrast to our knowledge about the anatomical development of the mammalian central auditory system, the development of its physiological properties is still poorly understood. In order to better understand the physiological properties of the developing mammalian auditory brainstem, we made intracellular recordings in brainstem slices from perinatal rats to examine synaptic transmission in the superior olivary complex, the first binaural station in the ascending auditory pathway. We concentrated on neurons in the lateral superior olive (LSO), which in adults, are excited from the ipsilateral side and inhibited from the contralateral side. Already at embryonic day (E) 18, when axon collaterals begin to invade the LSO anlage, synaptic potentials could be evoked from ipsilateral, as well as from contralateral inputs. Ipsilaterally elicited PSPs were always depolarizing, regardless of age. They had a positive reversal potential and could be completely blocked by the non-NMDA glutamate receptor antagonist CNQX. In contrast, contralaterally elicited PSPs were depolarizing from E18-P4, yet they turned into "adult-like," hyperpolarizing PSPs after P8. Their reversal potential shifted dramatically from -21.6 +/- 17.7 mV (E18-P0) to -73.0 +/- 7.1 mV (P10). Regardless of their polarity, contralaterally elicited PSPs were reversibly blocked by the glycine receptor antagonist strychnine. Bath application of glycine and its agonist beta-alanine further confirmed the transitory depolarizing action of glycine in the auditory brainstem. Since the transient excitatory behavior of glycine occurs during a period during which glycinergic synaptic connections in the LSO are refined by activity-dependent mechanisms, glycinergic excitation might be a mechanism by which synaptic rearrangement in the contralateral inhibitory pathway is accomplished.

Aging↗

PubMed1993

Pre- and postnatal development of efferent connections of the cochlear nucleus in the rat.

Although the connections of the auditory brainstem nuclei are well described in adult mammals, almost nothing is known concerning how and when these connections develop. The purpose of the present study was to describe the development of the efferent projections of the cochlear nucleus (CN), the first central relay station in the ascending auditory pathway of mammals. We used two tracers in rats aged between embryonic day 15 (E15) and postnatal day 14 (P14; birth in the rat is at E22 = P0). The carbocyanine dye DiI was applied into the CN in aldehyde-fixed tissue. The second tracer, biocytin, was applied into the ventral acoustic stria in an in vitro slice preparation. The ontogeny of the efferent projections from the CN could be divided into three periods. The first period (E15-E17) is characterized by axonal outgrowth. Axons traverse nuclei in the superior olivary complex and the lateral lemniscus and finally grow up into the inferior colliculus, but axon collaterals do not form during this period. The second period (E18-P5) is marked by pronounced collateral branching of CN fibers in auditory brainstem nuclei. Collateralisation in the contralateral inferior colliculus starts shortly before that in the ipsilateral superior olivary complex. The remaining auditory nuclei become successively innervated, as indicated by collaterals found in them. During the third period (P5-P14) terminal structures mature further, as shown by the morphological changes of the calyces of Held in the medial nucleus of the trapezoid body. In conclusion, our results show that the efferent connections from the cochlear nucleus form over a period of almost two weeks and are laid down without forming aberrant internuclear connections. On a nuclear level, an adult-like projection pattern is already achieved one week prior to the onset of physiological hearing.

Animals↗

PubMed1991

Auditory projections from the cochlear nucleus to pontine and mesencephalic reticular nuclei in the rat.

We investigated projections from the cochlear nucleus in the rat using the anterograde tracer Phaseolus vulgaris-leucoagglutinin. We focused on nuclei in the brainstem which are not considered to be part of the classical auditory pathway. In addition to labeling in auditory nuclei, we found presumed terminal fibers in 4 pontine and mesencephalic areas: (1) the pontine nucleus (PN), which receives bilateral projections from the antero- and posteroventral cochlear nuclei; (2) the ventrolateral tegmental nucleus (VLTg), which receives a contralateral projection from the rostral portion of the anteroventral cochlear nucleus; (3) the caudal pontine reticular nucleus (PnC), which receives bilateral input originating predominantly in the dorsal cochlear nucleus; and (4) the lateral paragigantocellular nucleus (LPGi), which receives projections from all subdivisions of the cochlear nuclei. In the VLTg and PnC, anterogradely labeled varicose axons were often found in close apposition to the primary dendrites and somata of large reticular neurons. Injections of the retrograde fluorescent tracer Fluoro-Gold into the VLTg demonstrated that the neurons of origin are mainly located contralaterally in the rostral anteroventral cochlear nucleus and in the cochlear root nucleus. The relevance of these auditory projections for short-latency audio-motor behaviors and acoustically elicited autonomic responses is discussed.

Animals↗

PubMed1990

Auditory projections to the inferior colliculus of the rat are present by birth.

Despite extensive literature on the anatomical organization of the adult mammalian auditory system, the ontogeny of internuclear connections is still obscure. We studied the postnatal development of afferent brainstem connections to the inferior colliculus in rat pups using WGA-HRP and DiI as tracers. At birth, connections to the inferior colliculus from the cochlear nuclei and nuclei of the superior olivary complexes and the lateral lemnisci are present. During successive development, there are no obvious changes in the quantity of labeled neurons or the basic labeling pattern. These results provide evidence that all input connections from auditory brainstem nuclei to the rat's inferior colliculus are established prenatally.

Aging↗