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M J Friedlander

Publications and source records attributed to M J Friedlander.

At least 19 recordsLinked to original sources
PubMed2001

Structure and projections of white matter neurons in the postnatal rat visual cortex.

Transient contributions of subplate neurons to the initial development of the cortex are well-characterized, yet little data are available on a subpopulation of subplate neurons that persist in the white matter (WM) of the cerebral cortex across development. To characterize the WM neurons, differential interference contrast and Nomarski optics were used to visualize individual cells in the WM in slices of rat visual cortex at postnatal ages 9-23. Soma-dendritic morphology and local axonal projection patterns, including probable synaptic innervation sites of their axons, were identified by intracellular filling with biocytin during electrophysiologic recordings. Dendritic branches of all WM neurons, tripartitioned here into upper, middle, and deep divisions, extend throughout the WM and frequently into the overlying cortex. Axonal arborizations from most WM neurons, including apparent boutons, project into adjacent WM with many also innervating overlying cortical layers, whereas some project into the stratum oriens/alveus of the hippocampal formation. Processes of a subset of WM neurons appear to be confined to the WM itself. By using antimicrotubule associated protein (MAP2) immunostaining to quantify the density of WM neurons in rat visual cortex, we find that their overall numbers decrease to approximately 30% of initial levels during postnatal development. During this same developmental period, an increasing percentage of WM neurons contain the synthetic enzyme for nitric oxide, nitric oxide synthase (NOS), as evaluated by immunostaining. Thus, WM neurons that survive the initial perinatal period of cell death are positioned under the laminae of the maturing cortex to potentially modulate the integration of visual signals through either conventional synaptic or nonconventional (diffusible NO signaling) mechanisms.

Action Potentials↗
PubMed2001

LTD induction in adult visual cortex: role of stimulus timing and inhibition.

One Hertz stimulation of afferents for 15 min with constant interstimulus intervals (regular stimulation) can induce long-term depression (LTD) of synaptic strength in the neocortex. However, it is unknown whether natural patterns of low-frequency afferent spike activity induce LTD. Although neurons in the neocortex can fire at overall rates as low as 1 Hz, the intervals between spikes are irregular. This irregular spike activity (and thus, presumably, irregular activation of the synapses of that neuron onto postsynaptic targets) can be approximated by stimulation with Poisson-distributed interstimulus intervals (Poisson stimulation). Therefore, if low-frequency presynaptic spike activity in the intact neocortex is sufficient to induce a generalized LTD of synaptic transmission, then Poisson stimulation, which mimics this spike activity, should induce LTD in slices. We tested this hypothesis by comparing changes in the strength of synapses onto layer 2/3 pyramidal cells induced by regular and Poisson stimulation in slices from adult visual cortex. We find that regular stimulation induces LTD of excitatory synaptic transmission as assessed by field potentials and intracellular postsynaptic potentials (PSPs) with inhibition absent. However, Poisson stimulation does not induce a net LTD of excitatory synaptic transmission. When the PSP contained an inhibitory component, neither Poisson nor regular stimulation induced LTD. We propose that the short bursts of synaptic activity that occur during a Poisson train have potentiating effects that offset the induction of LTD that is favored with regular stimulation. Thus, natural (i.e., irregular) low-frequency activity in the adult neocortex in vivo should not consistently induce LTD.

Action Potentials↗
PubMed1999

Arginine analogs modify signal detection by neurons in the visual cortex.

Nitric oxide (NO) modulates neurotransmitter release, induction of long-term synaptic potentiation and depression, and activity levels of neurons. However, it is not known whether NO contributes to the ability of the CNS to distinguish sensory signals from background noise and/or extract sensory information with greater reliability. We addressed these questions in the visual cortex, in vivo, using electrophysiological recording and analysis of signal detection from individual neurons. This was combined with microiontophoretic application of arginine analogs that either upregulate or downregulate the brain's endogenous NO-generating pathways or compounds that produce exogenous NO. Protocols that enhance NO levels generally increased the number of action potentials per trial evoked by visual stimuli, improved signal detection, and decreased the coefficient of variation of visually evoked responses, whereas NO-reducing protocols predominantly had complementary effects. Control experiments demonstrate that these effects are likely attributable to the specific ability of these arginine compounds to modify NO levels versus other nonspecific effects. Differential effects between neighboring cells and between single-cell receptive subfields suggest that these actions have a significant direct neural component versus exclusively operating indirectly on neurons through the central vascular actions of NO.

Action Potentials↗
PubMed1998

Dynamic modulation of cerebral cortex synaptic function by nitric oxide.

Our experiments demonstrate that NO exerts several actions in the cerebral cortex (see Fig. 4). Its production is mediated by neuronal activity through at least two pathways, NMDA receptors and AMPA receptors. By virtue of its diffusion in extracellular space, NO can interact with synapses that are near the production site but not necessarily anatomically connected to the NO source by a conventional synaptic linkage. NO's primary action is amplification of the release of the excitatory neurotransmitter, L-glutamate, thus effectively creating a positive feed-forward gain system. However, a number of effective brakes, presumably activated under physiological conditions, serve to limit the cascade. These include NO's ability to inhibit NMDA receptors, its negative feedback on the rate limiting enzyme, NOS (Rengasamy and Johns, 1993; Park et al., 1994; Ravichandran et al., 1995) and other inhibitory actions (Figs. 3H and L). Under conditions of extremely strong activation or curtailment of the inhibitory feedback mechanisms, as might occur with a change in the local redox milieu (see Lipton, this volume), the amplification cascade may proceed unchecked leading to neurotoxicity (see Dawson, this volume). NO's ability to modulate synaptic function is indicated by both its positive and negative modulatory role in a form of activity-dependent synaptic plasticity, covariance-induced synaptic potentiation. These opposing effects may be due to NO's ability to amplify glutamate release and inhibit NMDA receptors, respectively. The actions of endogenous NO in vivo are primarily facilitatory in visual cortex (Fig. 4). However, inhibitory actions also occur in vivo. The targets for NO in vivo, are potentially more diverse including the neurotransmitter release process, NMDA receptors, other receptors and ion channels and the cerebral vasculature. However, regardless of the signaling pathways, the net result of endogenous NO production in the intact visual cortex is a potent modulation of cells' responses to visual stimulation. Thus, it is likely that this signal plays an important role in ongoing information processing in the mature cerebral cortex, dynamically altering the effective strength of cortical networks.

Animals↗
PubMed1997

Transient synaptic potentiation in the visual cortex. I. Cellular mechanisms.

The cellular mechanisms that underlie transient synaptic potentiation were studied in visual cortical slices of adult guinea pigs (> or = age 5 wk postnatal). Postsynaptic potentials (PSPs) elicited by stimulation of the white matter/layer VI border were recorded with conventional intracellular techniques from layer II/III neurons. Transient potentiation (average duration 23 +/- 3 min, mean +/- SE) was evoked by 60 low-frequency (0.1 Hz) pairings of weak afferent stimulation with coincident intracellular depolarizing pulses (80 ms) of the postsynaptic cell. Fifty-one percent (47 of 92) of the pairing protocols led to significant enhancement (+26 +/- 3%) of the PSP peak amplitude. Blockade of action potential output from the recorded neuron during pairing with Lidocaine, N-ethyl bromide quaternary salt in the recording micropipette did not reduce the likelihood of potentiation (7 of 14 protocols = 50%). Thus transient synaptic potentiation does not require action potential output from the paired cell or recurrent synaptic activation in the local cortical circuit. Rather, the modification occurs at synaptic sites that directly impinge onto the activated neuron. Intracellular postsynaptic blockade of inhibitory PSPs only onto the paired cell with the chloride channel blocker 4,4'-dinitro-stilbene-2,2'-disulfonic acid and the potassium channel blocker cesium in he micropipette also did not reduce the likelihood of induction of potentiation (6 of 9 protocols = 67%). These results suggest that the potentiation is due to a true upregulation of excitatory synaptic transmission and that it does not require a reduction of inhibitory components of the compound PSP for induction. Chelation of postsynaptic intracellular calcium with 1,2-bis-2-aminophenoxy ethane-N,N,N',N'-tetraacetic acid (BAPTA) in all cases effectively blocked the induction of potentiation (no change in the PSP, 9 of 13 protocols; induction of synaptic depression, 4 of 13 protocols), suggesting that a rise in the intracellular postsynaptic calcium level is critical for the pairing-induced synaptic potentiation to occur. Bath application of the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV) reversibly blocked potentiation of the PSP peak amplitude in most cells (14 of 16) that were capable of significant potentiation of control solution. Blockade of nitric oxide production with bath application of the competitive inhibitor of nitric oxide synthase, L-nitro-arginine (LNA), did not significantly affect the likelihood of synaptic potentiation (11 of 20 cells). It did, however, block subsequent enhancement for several cells (2 of 4) that had previously had their inputs potentiated. Moreover, LNA increased the overall average magnitude of synaptic potentiation (with an additional +28%) when induction was successful. These results suggest that endogenous cortical nitric oxide production can both positively and negatively modulate this NMDA receptor-mediated type of synaptic plasticity.

Animals↗
PubMed1997

Transient synaptic potentiation in the visual cortex. II. Developmental regulation.

In our previous study, pairing-induced transient synaptic potentiation in supragranular layers of the visual cortex was described in mature guinea pigs. In the present study, the development of this type of synaptic plasticity and the underlying cellular mechanisms that mediate it were evaluated in animals from postnatal day (PND) 5 to 180. Potentiation is more reliably evoked in younger animals (likelihood: 75%, PND 5-30; 51%, PND > or = 34), and the magnitude of the effect is greater (+40 +/- 3%, mean +/- SE, PND 5-30; +26 +/- 3%, PND > or = 34). Similar to data obtained from the mature animals, visual cortical transient synaptic potentiation in the immature cortex occurs at excitatory synaptic sites directly activated by the stimulation, and activation by local recurrent cortical circuits is not necessary for the induction of this potentiation. This is demonstrated by 1) experiments in which action potential output from the paired neuron was blocked by Lidocaine, N-ethyl bromide quaternary salt applied into the neuron (5 of 5), and 2) experiments in which the contribution to the compound postsynaptic potential by inhibitory synapses was eliminated by selective, intracellular blockade by gamma-aminobutyric acid-mediated inhibitory postsynaptic potentials only onto the recorded neuron (7 of 11). Thus these perturbations do not reduce the likelihood or magnitude of this synaptic potentiation. In contrast to the N-methyl-D-aspartate (NMDA) receptor dependence for induction of this synaptic potentiation in the cortex of mature animals, in the young animals' cortices (PND 11-27) potentiation is readily induced during blockade of NMDA receptors (72%, 13 of 18, did not different from control: 75%, 40 of 53). Thus the NMDA receptor becomes functionally linked to a synaptic potentiation cascade during development, replacing another 2-amino-5-phosphonovaleric acid (APV)-insensitive potentiation process in the neonatal cortex. Postsynaptic intracellular calcium has a critical role in the induction of this form of synaptic potentiation in all ages studied. Synaptic potentiation was prevented (8 of 11 cases) or was replaced by synaptic depression (3 of 11 cells) in experiments in which postsynaptic calcium levels were reduced by intracellular application of 1,2-bis-2-aminophenoxy ethane-N,N,N',N'-tetraacetic acid (BAPTA) in the cortex of young (PND 7-14) animals, or in which the extracellular calcium concentrations was lowered. Inhibition of postsynaptic calcium-induced calcium release blocked synaptic potentiation (4 of 4 cells). Prolonged superfusion (3 h) of the nitric oxide synthase inhibitor L-nitro-arginine (LNA) did not significantly affect the likelihood (in LNA, 81%; 13 of 16 cells), or the magnitude (+38 +/- 7% increase in LNA vs. +40 +/- 3% in control cases) of potentiation, in contrast to its effects in the mature cortex.

Aging↗
PubMed1996

Developmental down-regulation of LTD in cortical layer IV and its independence of modulation by inhibition.

For in vitro LTD to remain viable as a model for synaptic weakening in visual cortical plasticity, it is crucial that it display a critical period for its induction within layer IV. A complicating factor, however, is that LTD in layer IV is modulated by inhibitory postsynaptic potentials (IPSPs); postsynaptic responses characterized as containing IPSPs do not depress in response to 1 Hz afferent stimulation. By blocking IPSPs intracellularly, we find that the ability to induce LTD in layer IV neurons is restored in juvenile, but not in mature animals. This developmental down-regulation of LTD induction is specific for layer IV when compared with LTD induction in layers II/III. These data are consistent with the hypothesis that an LTD-like phenomenon is involved in critical period plasticity and is apparently independent of developmental changes in inhibitory circuitry.

Animals↗
PubMed1996

Mechanisms for regulating synaptic efficiency in the visual cortex.

Brief epochs of pairing of low frequency synaptic activation and postsynaptic depolarization, in vitro, in supragranular neurons of nature guinea-pig visual cortex lead to a transient (20-60 min) synaptic potentiation. The process is due to a true up-regulation of excitatory synapse efficiency onto the activated neuron. The potentiation requires NMDA receptor activation and a postsynaptic calcium signal for induction and it is modifiable by endogenous nitric oxide (NO) production in the mature cortex. In the cortex of young animals (< PND 21), the pairing-induced potentiation is robust and depends on a postsynaptic calcium signal but it is independent of NMDA receptor activation and NO production. The ability of cortical synaptosomes to release endogenous glutamate is enhanced by NMDA receptor activation and this enhancement is NO-dependent. The NO signal, however, does not amplify the glutamate release of all synapses but only those that have activated voltage-gated calcium channels and were presumably more active at the time of the NO signal. Electrophysiological recordings from visual cortical neurons in anesthetized cats with local iontophoresis of compounds that inhibit or facilitate endogenous cortical NO production reveal the capacity for NO to modulate visual responses in vivo. NO appears to act in the intact cortex by amplifying signals of visual inputs that were co-active at the time of the NO production. The adult visual cortex is capable of dramatic alterations in synaptic efficiency over brief periods suggesting a dynamic cortical network. NMDA receptors and nitric oxide contribute to these processes.

Algorithms↗
PubMed1996

Intracellular blockade of inhibitory synaptic responses in visual cortical layer IV neurons.

1. Inhibitory postsynaptic potentials (IPSPs) evoked by stimulation at the white-matter/layer VI border were recorded intracellularly from visual cortical layer IV neurons maintained in vitro. These IPSPs, typically not apparent at resting membrane potentials, were measured at membrane potentials 15-25 mV depolarized from resting levels. The effects of two chloride channel blockers on these IPSPs were investigated. 2. 4,4'-Dinitro-stilbene-2,2'-disulfonic acid (DNDS) was found to inhibit IPSPs as it diffused into the postsynaptic cell from an intracellular micropipette, leaving only the presumed pure excitatory postsynaptic potential (EPSP) component of the evoked compound PSP. Input resistance, resting membrane potential, spike accommodation, and EPSPs at resting membrane potentials were not significantly affected. 3. A novel chloride channel blocker 5,11,17,23-tetrasulfonato-25,26,27,28-tetramethoxy-calix[4]a rene (TS-TM-calix[4]arene) was found to potently inhibit IPSPs recorded at depolarized membrane potentials. The TS-TM-calix[4]arene, similar to DNDS, did not affect input resistance, resting membrane potential, spike accommodation, and EPSPs at resting membrane potentials. 4. To confirm that DNDS and TS-TM-calix[4]arene were indeed blocking IPSPs, similar experiments were performed on monosynaptic IPSPs evoked by stimulation of layer V in the presence of 2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Both DNDS and TS-TM-calix[4]arene were effective in blocking monosynaptic IPSPs. 5. Consistent with the notion that DNDS and TS-TM-calix[4]arene block IPSPs by inhibiting gamma-aminobutyric acid-A (GABAA) receptor channels, the decrease in input resistance caused by extracellular application of muscimol was also significantly inhibited by intracellular use of these compounds. 6. These data suggest that DNDS and TS-TM-calix[4]arene applied intracellularly may be useful for the study of the function of GABAA-mediated synaptic inhibition of cortical neurons. Because only neurons impaled by the recording electrodes are influenced by the drugs, this method offers an advantage over extracellular application of GABAA blockers in that entire networks of neurons are not influenced.

Animals↗
PubMed1995

Localization of NADPH-diaphorase activity in the human visual cortex.

The present report describes the activity of NADPH-diaphorase (NADPHd) in area 17 of autopsied normal human visual cortex. Four human brains from autopsy tissue (4-8 h postmortem) were fixed by immersion in 4% paraformaldehyde in 0.1 M sodium phosphate buffer, pH 7.2-7.4, or in 10% formalin for 24 h. NADPHd histochemistry was done using the malic enzyme indirect method. The neuropile pattern of enzyme activity presented a clear six-layer appearance. Cell morphology and the laminar distribution of 73 NADPHd-positive neurons are described. All neurons found in area 17 of human cortex were sparsely spiny or smooth cells, located in all cortical layers except layer 4c. Quantitative analysis of the branching pattern of the dendritic tree was carried out. A symmetrical pattern was observed with no particular dendritic bias except for a few white matter and layer 1 cells. Larger dendritic fields were found in white matter cells when compared to the other cortical layers. Comparison of cell densities for gray and white matters showed that 85% of the NADPHd-positive neurons were located in the white matter. NADPHd was colocalized with nitric oxide synthase which produces nitric oxide, a short-life neuromediator implicated in synaptic plasticity, neuroprotection, and neurotoxicity. Thus, the spatial distribution of the NADPHd cells is important for posterior functional studies of the neuromediators in the brain.

Aged↗
PubMed1994

Role of NO production in NMDA receptor-mediated neurotransmitter release in cerebral cortex.

L-Glutamate and norepinephrine are examples of a major excitatory neurotransmitter and a neuromodulator in the cerebral cortex, respectively. Little is known of how chemical signaling between the anatomically distinct chemical pathways occurs. Specific activation of the N-methyl-D-aspartate (NMDA) class of glutamate receptor in synaptosomal preparations from guinea pig cerebral cortex caused release of both of these chemicals, and this release was blocked by agents that inhibit nitric oxide (NO) production or remove NO from the extracellular space. Furthermore, neurotransmitter release correlated with cortical NO production after NMDA receptor stimulation. These results suggest that NO production and its extracellular movement may be links in the pathway from NMDA receptor activation to changes in chemical signaling in surrounding synaptic terminals in the cerebral cortex.

Amino Acid Oxidoreductases↗
PubMed1994

Temporal covariance of pre- and postsynaptic activity regulates functional connectivity in the visual cortex.

1. It has been suggested from mathematical models and in vivo experiments in the visual cortex that periods of temporal covariance of pre- and postsynaptic activity can lead to a potentiation or depression of synaptic efficacy. We directly tested this hypothesis in vitro in the guinea pig and cat visual cortex. 2. Intracellular recordings were made in brain slices from 63 neurons in layers 2-4 in bicuculline-free artificial cerebrospinal fluid. Twenty-nine cells (n = 25 from pigmented guinea pigs and 4 from cats) were taken through a complete series of control and test protocols to evaluate the covariance hypothesis. Some (n = 7) cells that were taken through the complete experimental protocols were also filled intracellularly with biocytin. Compound postsynaptic potentials (PSPs) were evoked by low-frequency (0.2-1.0 Hz), weak (20% of threshold intensity) stimulation of the cortical white matter and/or intracortical sites in layers 2-3. 3. In one series of experiments we paired PSPs with imposed coincident depolarizing (S+) or hyperpolarizing (S-) pulses (mean +/- 2.8 nA for 50-80 ms) of the postsynaptic neuron (n = 54 PSPs; > 1 pairing protocol was often run on an individual cell). Controls consisted of analyzing the same number of S+ or S- pairings but with long temporal delays [called fixed delay pairings (FDPs)] between the test pathway stimulation and the onset of the intracellular current pulse (120 ms) and pseudopairings (PP) consisting of evoked PSPs and delivery of intracellular current injection pulses in a phase-independent manner. Twenty-one of 54 PSPs subjected to pairing were significantly modified by the protocol. The S+ protocol significantly (P < 0.05, Kolmogorov-Smirnov test) increased the peak amplitudes of 8 of 22 PSPs (+20 to +55%); the S- protocol significantly decreased the peak amplitudes of 13 of 32 PSPs (-15 to -88%), whereas the FDP and PP protocols generally did not cause significant changes in the PSPs (0% and 4%, respectively). Significant changes in PSPs persisted in most cases for 10-20 min. 4. Another series of experiments consisted of evaluating for the same cell the effects of evoking a PSP from one stimulation site without concomitant postsynaptic activation and alternately evoking a PSP from the other stimulation site with S+ or S- pairing (n = 25 PSPs). Only the paired pathway showed the predicted effects on the PSP (S+ pairing causing an increase in peak PSP amplitude and S- pairing causing a decrease in peak PSP amplitude).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Synaptic connections of physiologically identified geniculocortical axons in kitten cortical area 17.

Single geniculocortical axons were recorded in the cortical white matter of kittens and adult cats by using micropipettes filled with horseradish peroxidase (HRP). Of 41 axons recovered in 4-5 week old kittens, three well-filled axons arborized in area 17; the remainder were incomplete or arborized in area 18. One axon had Y-like physiological properties, two were X-like. They were recovered from two 34-day-old kittens. All three axons formed clustered arborizations, mainly in layer 4A. Electron microscopic (EM) analysis of 50 boutons from kitten and 38 boutons from adult controls revealed that the boutons from kitten made synapses more frequently on spines (91% of targets) than did the boutons from the adult (71%). One X-like axon in kitten also had a collateral projection that made synapses in layer 1; this has not been seen in adult cats. In overall extent, the axons from kitten fell within the adult range.

Aging↗
PubMed1992

Intracellular injections of permanent tracers in the fixed slice: a comparison of HRP and biocytin.

Here we describe a method for intracellularly injecting mixtures of the fluorescent dye Lucifer Yellow and the permanent tracers HRP or biocytin into aldehyde-fixed slices of the dorsal lateral geniculate nucleus in young postnatal cats. Lucifer Yellow was used for visual control in the injection procedure and the inclusion of HRP or biocytin allowed the subsequent use of simple histochemical processing to give a permanent record of the injected cells. Both tracer mixtures revealed the dendritic morphology of injected cells. However, HRP was found to be superior to biocytin, in that dendrites were better defined and fine details of cellular morphology such as spines were consistently revealed. Using this technique we were able to demonstrate that the dendritic morphology of geniculate cells is much more mature between birth and 2 weeks than was thought from previous studies using Golgi methods.

Animals↗
PubMed1991

Effects of monocular visual deprivation on geniculocortical innervation of area 18 in cat.

The effects of long-term monocular visual deprivation (MD) on the structure of the terminal arborizations of individual Y-type geniculocortical axons was studied in the cat's cortical area 18. Physiologically classified axons were filled with HRP by intracellular injection, and the three-dimensional distribution of the axons' terminal arborizations was quantified. Individual boutons observed at the light microscope (LM) level were verified as sites of synaptic contact by correlated light and electron microscopy (EM). Single boutons were serially sectioned and reconstructed for subsequent three-dimensional analysis. The arborizations of 17 Y-axons [6 normal (N), 6 nondeprived (ND), and 5 deprived (D)] were analyzed at the LM level, and 372 boutons (104 N, 129 ND, and 139 D) were fully reconstructed from serial sections for analysis at the EM level. MD leads to an expansion in the size of ND arborizations and a variable reduction in the size of the D arbors, which also have a higher bouton density than ND arborizations. ND axons form ectopic synapses, contacting proportionally more dendritic shafts than N or D boutons, and form more synapses per bouton, on average, than either N or D boutons. Compared to ND and N boutons, boutons of D axons are smaller, have fewer mitochondria, generally form synapses on a single target (usually dendritic spines), and occasionally make no synaptic contacts. The structural changes in the extent of individual axon arborizations may be the basis for change in ocular dominance column size with MD. However, the higher bouton density and variable effect on the extent of D axon arborization size suggest that considerable geniculocortical innervation from the deprived eye remains intact. The change in target preference for ND axons suggests that instead of a direct competition for postsynaptic sites by the developing geniculocortical axons innervated by the two retinas, the ND axon arborizations expand to invade synaptic space not normally occupied in such high proportion in the normal cortex. The severe changes in individual boutons following MD indicate that arborization size alone is not the only structural substrate underlying the altered responses of cortical neurons; changes in synaptic distribution onto target neurons may also play a role.

Animals↗
PubMed1991

Morphogenesis and territorial coverage by isolated mammalian retinal ganglion cells.

Identified retinal ganglion cells were isolated from postnatal cat retinas and their dendrites were removed by trituration and centrifugation. The denuded cells were placed in a cell culture system and allowed to reexpress dendritic arbors in the absence of afferent input, target tissue, and interactions with neighboring ganglion cells. The retinal ganglion cells were grown above a feeder layer of astrocytes on glass coverslips equipped with paraffin pedestals. The spatial patterns of the reexpressed neurites were quantitatively analyzed using a number of measures, including an estimate of the Hausdorff dimension, H, which was used as a scale-independent metric for how well the neurite patterns filled in a restricted spatial domain. As assessed by the estimation of the Hausdorff dimensions, the neurites from a single cell achieve uniform coverage of a restricted territory independent of the total neurite length or the total number of inter-branch-point segments. A comparison with H values of ganglion cells from the intact retina revealed a similar trend. These results suggest that these cultured ganglion cells can express an intrinsic growth strategy for the uniform coverage of a restricted territory. The arbors expressed in the culture system displayed a limited range of diameters and exhibited morphology similar to the alpha-, beta-, and gamma-ganglion cells of the intact retina in the absence of afferent input or the influences of neighboring cells and target tissue. Time-lapse video data revealed that individual cultured cells showed extensive dendritic remodeling during their growth; however, after about 3 d in culture, this remodeling did not appreciably affect the territorial coverage of a cell. In the intact retina, the existence of dendritic sheets that independently and uniformly sample visual space may result from this intrinsic ability to elaborate dendrites that uniformly cover or fill in a restricted territory.

Animals↗