Feedback Neurons Research Articles

A mechanism underlying mature-onset obesity: evidence from the hyperphagic phenotype of brain-derived neurotrophic factor mutants

Mice deficient in brain-derived neurotrophic factor (BDNF) develop mature-onset obesity, primarily due to overeating. To gain insight into the mechanism of this hyperphagia, we characterized food intake, body weight, meal pattern, and meal microstructure in young and mature mice fed balanced or high-fat diets. Hyperphagia and obesity occurred in mature but not young BDNF mutants fed a balanced diet. This hyperphagia was mediated by increased meal number, which was associated with normal meal size, meal duration, and satiety ratio. In contrast, the high-fat diet induced premature development of hyperphagia and obesity in young BDNF mutants and a similar magnitude hyperphagia in mature mutants. This hyperphagia was supported by increased meal size and was accompanied by a reduced satiety ratio. Thus the mechanism underlying hyperphagia was present before significant weight gain, but whether it occurred, and whether meal frequency or meal size was altered to support it, was modulated by a process associated with aging and by diet properties. Meal pattern changes associated with the balanced diet suggested meal initiation, and the oropharyngeal positive feedback that drives feeding, were enhanced and might have contributed to overeating in BDNF mutants, whereas negative feedback was normal. Consistent with this hypothesis, meal microstructure revealed that all hyperphagic mutant groups exhibited increased intake rates at meal onset. Therefore, the central nervous system targets of BDNF actions may include orosensory brain stem neurons that process and transmit positive feedback or forebrain neurons that modulate its strength.

Electric signaling behavior and the mechanisms of electric organ discharge production in mormyrid fish

Mormyrid fish communicate and navigate using electric organ discharges (EODs). The EOD is highly stereotyped and provides information on sender identity, including species, sex, reproductive condition, and possibly relative status and individual identity. By contrast, the sequence of pulse intervals (SPI) is variable and plays more of a role in signaling behavioral states. Various types of SPI displays may be produced, including tonic patterns such as ‘random’ and ‘regularized’, and phasic patterns such as ‘bursts’ and ‘cessations’. Certain displays have been linked to specific behaviors such as aggression, submission, courtship and active exploration. In addition, interacting pairs of fish may produce stereotyped displays involving the relative timing of their EODs. The EOD waveform is controlled by the morphological and physiological properties of cells in the electric organ termed electrocytes. Differences in the innervation, morphology, size and membrane characteristics of electrocytes have been directly linked to species and sex differences in the EOD. The generation of each EOD is initiated in the medullary command nucleus (CN), which thereby determines the timing of EOD output. CN does not have any properties of a pacemaker, but rather appears to integrate descending inputs that affect the probability of EOD production. The precommand nucleus (PCN) provides a major source of excitatory input to CN and is itself inhibited by corollary discharge feedback following the production of each EOD. Changes in the activity of PCN and its inhibitory feedback neurons modify EOD output, and therefore drive the generation of SPI patterns. Current studies are addressing the mechanisms underlying the generation of these patterns and preliminary results suggest that different types of signals may be controlled by distinct components of the electromotor system. This is similar to findings in other electrogenic teleosts, suggesting that it may be a general feature in the motor control of signaling behavior.

Subthalamo-pallido-striatal axis: a feedback system in the basal ganglia.

Systemic administration of a dopamine D2 receptor blocker, haloperidol, but not vehicle, significantly increased the number of c-Fos-immunoreactive neurons in the globus pallidus (GP) in rats. Dual immunohistochemistry, a combination of c-Fos immunohistochemistry and retrograde tracing experiments with cholera toxin B (ChB), revealed that a subset of the c-Fos-immunoreactive GP neurons was pallidostriatal feedback neurons. Lesioning of the subthalamic nucleus (STN) by local injection of ibotenic acid inhibited the haloperidol-induced c-Fos expression in the GP neurons, suggesting that the activation of GP neurons is a result of increased excitatory drives from the STN. Therefore, the present findings are evidence of the existence of the subthalamo-pallido-striatal axis as a feedback system in the internal circuits of the basal ganglia.

Physiological properties and response modulations of mushroom body feedback neurons during olfactory learning in the honeybee, Apis mellifera

Mushroom bodies are central brain structures and essentially involved in insect olfactory learning. Within the mushroom bodies γ-aminobutyric acid (GABA)-immunoreactive feedback neurons are the most prominent neuron group. The plasticity of inhibitory neural activity within the mushroom body was investigated by analyzing modulations of odor responses of feedback neurons during olfactory learning in vivo. In the honeybee, Apis mellifera, feedback neurons were intracellularly recorded at their neurites. They produced complex patterns of action potentials without experimental stimulation. Summating postsynaptic potentials indicate that their synaptic input region lies within the lobes. Odor and antennal sucrose stimuli evoked excitatory phasic-tonic responses. Individual neurons responded to various odors; responses of different neurons to the same odor were highly variable. Response modulations were determined by comparing odor responses of feedback neurons before and after one-trial olfactory conditioning or sensitisation. Shortly after pairing an odor stimulus with a sucrose reward, odor-induced spike activity of feedback neurons decreased. Repeated odor stimulations alone, equally spaced as in the conditioning experiment, did not affect the odor-induced excitation. A single sensitisation trial also did not alter odor responses. These findings indicate that the level of odor-induced inhibition within the mushroom bodies is specifically modulated by experience.

Morphology of feedback neurons in the mushroom body of the honeybee, Apis mellifera

The anatomy of gamma-aminobutyric acid (GABA)-immunoreactive, recurrent feedback neurons in the mushroom body (MB) of the honeybee, Apis mellifera, was investigated by using intraneuropilar injections of cobalt ions and light microscopic techniques. Each MB contains approximately 110 GABA-immunoreactive neurons, and approximately 50% of them are feedback neurons, i.e., they connect the MB output regions--the alpha-lobe, beta-lobe, and pedunculus--with its input regions--the calyces. Their somata are located in the lateral protocerebral lobe, and their primary neurites project medially and bifurcate near the alpha-lobe. In the alpha-lobe feedback neurons form narrow banded, horizontal arborizations in the dorsal and median alpha-lobe; each cell innervates a certain alpha-lobe layer. The neurons form additional branches in the pedunculus and the beta-lobe. All calycal subcompartments--the lip, collar, and basal ring--are innervated by feedback neurons. However, individual feedback neurons innervate exclusively a certain subcompartment in both the median and lateral calyx. Due to the arrangement of intrinsic Kenyon cells, each calycal subcompartment is connected to its specific, corresponding layer in the alpha-lobe. Feedback neurons interconnect the alpha-lobe and the calyces in either a corresponding or a noncorresponding fashion. With respect to their branching pattern in the alpha-lobe, the basal ring and the collar neuropil receive input from feedback neurons innervating the corresponding dorsal and median alpha-lobe layers. By contrast, the lip region, which receives olfactory antennal input, is innervated by feedback neurons with arborizations in a noncorresponding dorsal alpha-lobe layer.

Morphology of feedback neurons in the mushroom body of the honeybee, Apis mellifera.

The anatomy of gamma-aminobutyric acid (GABA)-immunoreactive, recurrent feedback neurons in the mushroom body (MB) of the honeybee, Apis mellifera, was investigated by using intraneuropilar injections of cobalt ions and light microscopic techniques. Each MB contains approximately 110 GABA-immunoreactive neurons, and approximately 50% of them are feedback neurons, i.e., they connect the MB output regions--the alpha-lobe, beta-lobe, and pedunculus--with its input regions--the calyces. Their somata are located in the lateral protocerebral lobe, and their primary neurites project medially and bifurcate near the alpha-lobe. In the alpha-lobe feedback neurons form narrow banded, horizontal arborizations in the dorsal and median alpha-lobe; each cell innervates a certain alpha-lobe layer. The neurons form additional branches in the pedunculus and the beta-lobe. All calycal subcompartments--the lip, collar, and basal ring--are innervated by feedback neurons. However, individual feedback neurons innervate exclusively a certain subcompartment in both the median and lateral calyx. Due to the arrangement of intrinsic Kenyon cells, each calycal subcompartment is connected to its specific, corresponding layer in the alpha-lobe. Feedback neurons interconnect the alpha-lobe and the calyces in either a corresponding or a noncorresponding fashion. With respect to their branching pattern in the alpha-lobe, the basal ring and the collar neuropil receive input from feedback neurons innervating the corresponding dorsal and median alpha-lobe layers. By contrast, the lip region, which receives olfactory antennal input, is innervated by feedback neurons with arborizations in a noncorresponding dorsal alpha-lobe layer.

Physiology and morphology of olfactory neurons associating with the protocerebral lobe of the honeybee brain

Physiology and morphology of olfactory neurons associated with the protocerebral lobe around the α-lobe of the mushroom body were studied in the brain of the honeybee Apis mellifera using intracellular recording and staining techniques. The responses of neurons to behaviorally relevant odorants (a blend, and components of the Nasonov pheromone, and some other non-pheromonal odors) were recorded. Different response patterns were observed within different neurons, and often within the same neuron, in response to different stimuli. All the neurons stained had innervations in the protocerebral lobe. The cell profiles varied from cells connecting the antennal lobe with both the protocerebral and lateral protocerebral lobes (projection neurons), cells linking the pedunculus of the mushroom body with both the protocerebral and lateral protocerebral lobes (PE1 neurons), cells linking the α-lobe and protocerebral lobe with the calyces of the mushroom body (feedback neurons), and cells linking the α-lobe and protocerebral lobe with the antennal lobe (recurrent neurons), to cells connecting the protocerebral lobe with the contralateral protocerebrum (bilateral neurons). These findings suggest that the protocerebral lobe acts as an olfactory center associating with other centers, and provides multi-layered recurrent networks within the protocerebrum and between the deutocerebrum and the protocerebrum in honeybee olfactory pathways.

Area-specific laminar distribution of cortical feedback neurons projecting to cat area 17: quantitative analysis in the adult and during ontogeny.

Corticocortical pathways can be classified as feedback and feedforward, in part according to the laminar distribution of the parent cell bodies. Here, we have developed exhaustive sampling procedures to determine unambiguously this laminar distribution. This shows that individual extrastriate areas in the adult cat have highly stereotyped proportions of supragranular layer neurons with respect to the total population of neurons back-projecting to area 17. During development, these adult laminar patterns emerge from an initially uniform radial distribution through a process of selective reorganization, which is highly specific to each area. Injections of fluorescent retrograde tracers were made in area 17. In areas 19, 20, posteromedial lateral suprasylvian area, and anteromedial lateral suprasylvian area, we defined a projection zone as the region containing retrogradely labeled neurons. In the neonate, counts of labeled neurons throughout the projection zones show constant percentages of 40% in the supragranular layers. During development, there is an area-specific reduction in the percentage of supragranular labeled neurons generating the laminar distributions characteristic of each area. Numbers of labeled neurons were estimated at different eccentricities of the projection zone. This finding indicates that during development there is a relative decrease in the numbers of labeled neurons of the periphery of the projection zone in the supragranular layers but not in the infragranular layers. This decrease is accompanied by a relative decrease in the dimensions of the supragranular projection zone with respect to the infragranular projection zone. These findings suggest that each extrastriate area precisely adjusts the proportions of supragranular layer neurons back-projecting to striate cortex in part by developmental changes in the divergence-convergence values of individual neurons. This shaping of corticocortical connectivity occurs relatively late in postnatal development and could, therefore, be under epigenetic control.

Presynaptic Versus Postsynaptic Localization of μ and δ Opioid Receptors in Dorsal and Ventral Striatopallidal Pathways

Parallel studies have demonstrated that enkephalin release from nerve terminals in the pallidum (globus pallidus and ventral pallidum) can be modulated by locally applied opioid drugs. To investigate further the mechanisms underlying these opioid effects, the present study examined the presynaptic and postsynaptic localization of delta (DOR1) and mu (MOR1) opioid receptors in the dorsal and ventral striatopallidal enkephalinergic system using fluorescence immunohistochemistry combined with anterograde and retrograde neuronal tracing techniques. DOR1 immunostaining patterns revealed primarily a postsynaptic localization of the receptor in pallidal cell bodies adjacent to enkephalin- or synaptophysin-positive fiber terminals. MOR1 immunostaining in the pallidum revealed both a presynaptic localization, as evidenced by punctate staining that co-localized with enkephalin and synaptophysin, and a postsynaptic localization, as evidenced by cytoplasmic staining of cells that were adjacent to enkephalin and synaptophysin immunoreactivities. Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) or the retrograde tracer Texas Red-conjugated dextran amine (TRD) into the dorsal and ventral striatum resulted in labeling of striatopallidal fibers and pallidostriatal cell bodies, respectively. DOR1 immunostaining in the pallidum co-localized only with TRD and not PHA-L, whereas pallidal MOR1 immunostaining co-localized with PHA-L and not TRD. These results suggest that pallidal enkephalin release may be modulated by mu opioid receptors located presynaptically on striatopallidal enkephalinergic neurons and by delta opioid receptors located postsynaptically on pallidostriatal feedback neurons.

A dynamic K-winners-take-all neural network

In this paper, a dynamic K-winners-take-all (KWTA) neural network, which can quickly identify the K-winning neurons whose activations are larger than the remaining ones, is proposed and analyzed. For N competitors, the proposed KWTA network is composed of N feedforward hardlimit neurons and three feedback neurons, which are used to determine the dynamic threshold. From theoretical analysis and simulation results, we found that the convergence of the proposed KWTA network, which requires Log(2)(N+1) iterations in average to complete a KWTA process, is independent of K, the number of the desired winners, and faster than that of the existing KWTA networks.

Neurofilament protein is differentially distributed in subpopulations of corticocortical projection neurons in the macaque monkey visual pathways

Previous studies of the primate cerebral cortex have shown that neurofilament protein is present in pyramidal neuron subpopulations displaying specific regional and laminar distribution patterns. In order to characterize further the neurochemical phenotype of the neurons furnishing feedforward and feedback pathways in the visual cortex of the macaque monkey, we performed an analysis of the distribution of neurofilament protein in corticocortical projection neurons in areas V1, V2, V3, V3A, V4, and MT. Injections of the retrogradely transported dyes Fast Blue and Diamidino Yellow were placed within areas V4 and MT, or in areas V1 and V2, in 14 adult rhesus monkeys, and the brains of these animals were processed for immunohistochemistry with an antibody to nonphosphorylated epitopes of the medium and heavy molecular weight subunits of the neurofilament protein. Overall, there was a higher proportion of neurons projecting from areas V1, V2, V3, and V3A to area MT that were neurofilament protein-immunoreactive (57–100%), than to area V4 (25–36%). In contrast, feedback projections from areas MT, V4, and V3 exhibited a more consistent proportion of neurofilament protein-containing neurons (70–80%), regardless of their target areas (V1 or V2). In addition, the vast majority of feedback neurons projecting to areas V1 and V2 were located in layers V and VI in areas V4 and MT, while they were observed in both supragranular and infragranular layers in area V3. The laminar distribution of feedforward projecting neurons was heterogeneous. In area V1, Meynert and layer IVB cells were found to project to area MT, while neurons projecting to area V4 were particularly dense in layer III within the foveal representation. In area V2, almost all neurons projecting to areas MT or V4 were located in layer III, whereas they were found in both layers II–III and V–VI in areas V3 and V3A. These results suggest that neurofilament protein identifies particular subpopulations of corticocortically projecting neurons with distinct regional and laminar distribution in the monkey visual system. It is possible that the preferential distribution of neurofilament protein within feedforward connections to area MT and all feedback projections is related to other distinctive properties of these corticocortical projection neurons. © 1996 Wiley-Liss, Inc.

Neurofilament protein is differentially distributed in subpopulations of corticocortical projection neurons in the macaque monkey visual pathways.

Previous studies of the primate cerebral cortex have shown that neurofilament protein is present in pyramidal neuron subpopulations displaying specific regional and laminar distribution patterns. In order to characterize further the neurochemical phenotype of the neurons furnishing feedforward and feedback pathways in the visual cortex of the macaque monkey, we performed an analysis of the distribution of neurofilament protein in corticocortical projection neurons in areas V1, V2, V3, V3A, V4, and MT. Injections of the retrogradely transported dyes Fast Blue and Diamidino Yellow were placed within areas V4 and MT, or in areas V1 and V2, in 14 adult rhesus monkeys, and the brains of these animals were processed for immunohistochemistry with an antibody to nonphosphorylated epitopes of the medium and heavy molecular weight subunits of the neurofilament protein. Overall, there was a higher proportion of neurons projecting from areas V1, V2, V3, and V3A to area MT that were neurofilament protein-immunoreactive (57-100%), than to area V4 (25-36%). In contrast, feedback projections from areas MT, V4, and V3 exhibited a more consistent proportion of neurofilament protein-containing neurons (70-80%), regardless of their target areas (V1 or V2). In addition, the vast majority of feedback neurons projecting to areas V1 and V2 were located in layers V and VI in areas V4 and MT, while they were observed in both supragranular and infragranular layers in area V3. The laminar distribution of feedforward projecting neurons was heterogeneous. In area V1, Meynert and layer IVB cells were found to project to area MT, while neurons projecting to area V4 were particularly dense in layer III within the foveal representation. In area V2, almost all neurons projecting to areas MT or V4 were located in layer III, whereas they were found in both layers II-III and V-VI in areas V3 and V3A. These results suggest that neurofilament protein identifies particular subpopulations of corticocortically projecting neurons with distinct regional and laminar distribution in the monkey visual system. It is possible that the preferential distribution of neurofilament protein within feedforward connections to area MT and all feedback projections is related to other distinctive properties of these corticocortical projection neurons.

Memory and Transfer of Information

Memory and Transfer of Information