Sex-specific effects of prenatal stress on neuronal development in the medial prefrontal cortex and the hippocampus.

Evidence suggests that maternal stress during gestation in humans and animals can cause emotional and cognitive dysfunction in the offspring. In the present study, we examined neurons of the hippocampus and the medial prefrontal cortex of adult rats exposed to prenatal stress. Using a revised Golgi-Cox staining method, we found decreases in dendritic length and complexity in area CA3 and the dentate gyrus of male rats exposed to prenatal stress compared with the controls, as well as decreased dendritic complexity in the prelimbic cortex. In contrast, we did not detect any changes in dendrites of female rats exposed to prenatal stress. Our results suggest that prenatal stress can induce long-lasting morphological changes in the medial prefrontal cortex and the hippocampus that are sex specific.

Cocaine enhances resistance to extinction of responding for brain-stimulation reward in adult prenatally stressed rats.

The present experiment assessed whether prenatal stress (PS) can alter the ability of acute and chronic cocaine administration to increase and decrease the rewarding effectiveness of the medial forebrain bundle (MFB) using intracranial self-stimulation (ICSS), and also whether PS can affect the extinction of the MFB stimulation response. Adult male offspring of female rats that received PS or no PS (nPS) were implanted with MFB stimulating electrodes, and were then tested in ICSS paradigms. In both nPS and PS offspring, acute cocaine injection decreased ICSS thresholds dose-dependently. However, the threshold-lowering effects at any dose were not significantly different between groups. There was also no group-difference in the threshold-elevating effects of chronic cocaine administration. Nevertheless, chronically drug-administered PS rats exhibited a resistance to the extinguishing of the response for brain-stimulation reward when acutely treated with cocaine, as compared to extinction without cocaine treatment. The results suggest that PS may weaken the ability for response inhibition under cocaine loading in male adult offspring.

Adult hippocampal neurogenesis in rodents and primates: endogenous, enhanced, and engrafted.

Since the studies of Ramon y Cajal, a central postulate in neuroscience has been the view that the adult brain lacks the ability to regenerate its neurons. This dogma has been challenged in the last few decades, and mounting evidence has accumulated showing the existence of a phenomenon designated 'adult neurogenesis'. De novo generation of neurons by neural progenitor cells in the adult brain is thought to be preserved only in restricted brain areas, such as the hippocampal dentate gyrus (DG) and the subventricular zone (SVZ) of the lateral ventricle. Data in the last decade coming mostly from rodent models have clearly documented that precursor cells residing in the anterior portion of SVZ and the subgranular zone of DG are responsible for adding new neurons in the olfactory bulb and DG, respectively. This raised significant interest in the clinical potential of neural progenitor cells, and recent studies have documented that brain injury is capable of activating an endogenous program of neurogenesis resulting in neuronal replacement in various cerebral regions of rodents and primates. If the newly generated neurons in the adult brain prove to be functional, it could have a tremendous impact for cell replacement therapies. Here, we summarize current knowledge of the mechanisms affecting adult hippocampal neurogenesis in both rodents and primates, and discuss its implications in developing novel strategies for the treatment of human neurological diseases.

Impairments in recognition memory for object and for location after transient brain ischemia in monkeys.

Using an object recognition or location memory test employing either small or large sets of training stimuli, we examined the effects of selective damage to the hippocampus after ischemia in Japanese monkeys. Ischemic (ISC) monkeys were significantly impaired in learning a delayed matching-to-sample (DMS) task (10 sec) when the sample and test objects were drawn from a set of 45 possible stimuli, but not in learning a DMS when a set of 300 possible stimuli was used ISC monkeys were also impaired in a delayed matching-to-location (DML) task that employed a 3-well tray but not in one that employed a 10-well tray. After criterion learning was attained, ISC monkeys were impaired significantly only in the 300-stimuli version and at the longest delay tested (10 min). These results suggest that the hippocampus might be involved in processing comparisons and forming relationships between current and recent stimuli, but not in the remembering of familiar objects, and in long-term maintenance (more than 10 min) of stimulus memory.

Distinctive morphology of hippocampal CA1 terminations in orbital and medial frontal cortex in macaque monkeys.

The fine morphology of hippocampal connections to the orbital and medial frontal cortex (OMFC) was investigated by placing injections of anterograde tracers in the CA1 in two monkeys. The axons terminated mainly in layers 2 and 3, of areas 11, 13, 14c, 25, and 32, and were widely divergent in these layers, traversing 2-4 mm. Boutons were scattered along the main axon, but also occurred as distinctive small, spherical clusters of terminations ("mini-clusters"; diameter <50 microm). Occasional larger terminal arbors were observed in layer 3 and these were often unusually tortuous or convoluted. These features may imply a specialized microcircuitry of hippocampal-OMFC connections, including an origin from a particular subpopulation of CA1 projection neurons.

Direct projections from CA1 to the superior temporal sulcus in the monkey, revealed by single axon analysis.

Anterograde tracer injections in the middle sector of CA1 in macaque monkeys demonstrate a direct projection to the fundus of the anterior superior temporal sulcus, in area IPa. Terminations are predominantly in layer 3. With regard to both terminal and arbor configuration, these hippocampal-cortical connections are morphologically similar to corticocortical connections to temporal association cortex. This report provides additional evidence of direct CA1 connections to particular multimodal cortical areas.

Differential thalamic connections of the posteroventral and dorsal posterior cingulate gyrus in the monkey.

Previous functional studies suggest that the posterior cingulate gyrus is involved in spatial memory and its posteroventral part, in particular, is also involved in auditory memory. However, it is not clear whether the neural connections of the posteroventral part differ from those of the rest of the posterior cingulate gyrus. Here, we describe the thalamic connections of the posteroventral part of monkey area 23b (pv-area 23b), the main component of the posteroventral posterior cingulate gyrus. We compare these thalamic connections with those of the more dorsal area 23b (d-area 23b) and of adjoining retrosplenial areas 29 and 30. Thalamocortical projections to pv-area 23b originate mainly from the anterior nuclei, nucleus lateralis posterior and medial pulvinar. In contrast, projections to d-area 23b originate from the nucleus lateralis posterior, medial pulvinar, nucleus centralis latocellularis, mediodorsal nucleus and nucleus ventralis anterior and lateralis and weakly from the anterior nuclei. Projections to retrosplenial areas 29 and 30 originate from the anterior nuclei. Corticothalamic projections from pv-area 23b terminate in the anterior and laterodorsal nuclei, nucleus lateralis posterior and medial pulvinar. Projections from d-area 23b terminate in these nuclei as well as the nucleus ventralis anterior and lateralis. Projections from area 30 terminate mainly in the anterior nuclei and, to a lesser extent, in the medial pulvinar. These results show that the connections of pv-area 23b differ from those of d-area 23b or areas 29 and 30. This suggests that pv-area 23b may play distinct functional roles in memory processes, such as spatial and auditory memory.

Connections between the amygdala and auditory cortical areas in the macaque monkey.

Connections between the amygdala and auditory cortical areas TC, and the rostral, intermediate and caudal regions of area TA (TAr, TAi and TAc, respectively) in the macaque monkey (Macaca fuscata and Macaca nemestrina) were investigated following placements of cortical deposits of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP). Areas TC and TAc received weak projections and these derived only from the lateral basal nucleus. Areas TAi and TAr received projections from the lateral, lateral basal and accessory basal nuclei. In contrast, corticopetal projections to the amygdala originated in areas TAi and TAr, but never in TAc or TC. The projections from areas TAi and TAr terminated only in the lateral nucleus, and in particular at the lateral part of the middle and caudal portions of the amygdala. Thus, the amygdalofugal projections to the auditory cortices are more widespread and more complex than the amygdalopetal projections of the auditory cortices. As judged from experiments in which deposits were made at different sites along the rostrocaudal axis of the auditory cortex, there was a progressive increase seen in density of the amygdala connections with more anteriorly-placed injection sites.